Use of genomic signatures to predict responsiveness of patients with prostate cancer to post-operative radiation therapy

ABSTRACT

Methods, compositions, and kits for identifying individuals who will be responsive to post-operative radiation therapy for treatment of prostate cancer are disclosed. In particular, the invention relates to a genomic signature based on expression levels of DNA Damage Repair genes that can be used to identify individuals likely to benefit from post-operative radiation therapy after a prostatectomy.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. Pat. Application No.16/327,260, filed Feb. 21, 2019, which is the U.S. National Phase of PCTApplication No. PCT/US2017/048486, filed Aug. 24, 2017, which claimsbenefit of priority under 35 U.S.C. §119(e) of U.S. Serial No.62/379,178, filed Aug. 24, 2016, the entire contents of which isincorporated herein by reference in its entirety.

INCORPORATION OF SEQUENCE LISTING

The material in the accompanying sequence listing is hereby incorporatedby reference into this application. The accompanying sequence listingfile, name GENDX_014C1_Sequence_Listing.xml, was created on Aug. 15,2002, and is 1.69 MB.

FIELD OF THE INVENTION

The present invention pertains to the field of personalized medicine andmethods for treating prostate cancer. In particular, the inventionrelates to the use of genomic signatures to identify individuals in needof treatment for prostate cancer who will be responsive topost-operative radiation therapy.

BACKGROUND OF THE INVENTION

Cancer is the uncontrolled growth of abnormal cells anywhere in a body.The abnormal cells are termed cancer cells, malignant cells, or tumorcells. Many cancers and the abnormal cells that compose the cancertissue are further identified by the name of the tissue that theabnormal cells originated from (for example, prostate cancer). Cancercells can proliferate uncontrollably and form a mass of cancer cells.Cancer cells can break away from this original mass of cells, travelthrough the blood and lymph systems, and lodge in other organs wherethey can again repeat the uncontrolled growth cycle. This process ofcancer cells leaving an area and growing in another body area is oftentermed metastatic spread or metastatic disease. For example, if prostatecancer cells spread to a bone (or anywhere else), it can mean that theindividual has metastatic prostate cancer.

Standard clinical parameters such as tumor size, grade, lymph nodeinvolvement and tumor-node-metastasis (TNM) staging (American JointCommittee on Cancer) may correlate with outcome and serve to stratifypatients with respect to (neo)adjuvant chemotherapy, immunotherapy,antibody therapy and/or radiotherapy regimens. Incorporation ofmolecular markers in clinical practice may define tumor subtypes thatare more likely to respond to targeted therapy. However, stage-matchedtumors grouped by histological or molecular subtypes may responddifferently to the same treatment regimen. Additional key genetic andepigenetic alterations may exist with important etiologicalcontributions. A more detailed understanding of the molecular mechanismsand regulatory pathways at work in cancer cells and the tumormicroenvironment (TME) could dramatically improve the design of novelanti-tumor drugs and inform the selection of optimal therapeuticstrategies. The development and implementation of diagnostic, prognosticand therapeutic biomarkers to characterize the biology of each tumor mayassist clinicians in making important decisions with regard toindividual patient care and treatment.

This background information is provided for the purpose of making knowninformation believed by the applicant to be of possible relevance to thepresent invention. No admission is necessarily intended, nor should beconstrued, that any of the preceding information constitutes prior artagainst the present invention.

SUMMARY OF THE INVENTION

The present invention is based on the discovery of a genomic signaturethat is useful for identifying individuals who will be responsive topost-operative radiation therapy for treatment of prostate cancer. Inparticular, the invention relates to a genomic signature based onexpression levels of DNA damage repair genes that can be used toidentify individuals likely to benefit from post-operative radiationtherapy after a prostatectomy. The methods of the present invention areuseful for generating a Post-Operative Radiation Therapy Outcome Score(PORTOS) to predict response to radiation therapy in prostate cancerpatients.

In one aspect, the invention includes a method of predicting response topost-operative radiation therapy for prostate cancer, the methodcomprising: a) providing a biological sample comprising prostate cancercells from a subject; b) assaying a level of expression of a pluralityof genes in the biological sample, wherein said plurality of genescomprises one or more genes selected from the group consisting of DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11,CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2,PLK2, EME1, and BIN2; c) calculating a post-operative radiation therapyoutcome score (PORTOS) based on the levels of expression of theplurality of genes in the biological sample to determine whether or notthe subject is likely to benefit from the post-operative radiationtherapy. A PORTOS greater than 0 (i.e., high PORTOS) indicates that asubject will benefit from post-operative radiation therapy, whereas aPORTOS of less than or equal to 0 (i.e., low PORTOS) indicates that asubject will not benefit from post-operative radiation therapy.

In one embodiment, the plurality of genes comprises at least 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or24 genes selected from the group consisting of DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, andBIN2. In another embodiment, the plurality of genes comprises DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11,CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2,PLK2, EME1, and BIN2. In another embodiment, the plurality of genes isselected from DRAM1 and KRT14; DRAM1, KRT14 and PTPN22; DRAM1, KRT14,PTPN22 and ZMAT3; DRAM1, KRT14, PTPN22, ZMAT3 and ARHGAP15; DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15 and IL1B; DRAM1, KRT14, PTPN22, ZMAT3,ARHGAP15, IL1B and ANLN; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B,ANLN and RPS27A; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A and MUM1; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A, MUM1 and TOP2A; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B,ANLN, RPS27A, MUM1, TOP2A and GNG11; DRAM1, KRT14, PTPN22, ZMAT3,ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11 and CDKN3; DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11,CDKN3 and HCLS1; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1 and DTL; DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL and IL7R; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A,MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R and UBA7; DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3,HCLS1, DTL, IL7R, UBA7 and NEK1; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15,IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7,NEK1 and CDKN2AIP; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1,CDKN2AIP and APEX2; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1,CDKN2AIP, APEX2 and KIF23; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B,ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1,CDKN2AIP, APEX2, KIF23 and SULF2; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15,IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7,NEK1, CDKN2AIP, APEX2, KIF23, SULF2 and PLK2; DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2 and EME1; andDRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A,GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23,SULF2, PLK2, EME1 and BIN2.

In certain embodiments, the method is performed after the patientundergoes a radical prostatectomy. The method is preferably performedprior to treatment of the subject with radiation therapy to determine ifthe subject will benefit from radiation therapy or should beadministered some other anti-cancer treatment (e.g., chemotherapy,immunotherapy, hormonal therapy, biologic therapy, or a combinationthereof). The method may also be performed while the subject isundergoing radiation therapy to help evaluate whether continuedtreatment is likely to be efficacious.

The biological sample obtained from a patient is typically a biopsy ortumor sample, but can be any sample from bodily fluids or tissue of thepatient that contains cancerous cells. In certain embodiments, nucleicacids comprising sequences from genes selected from the group consistingof DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1,TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2,KIF23, SULF2, PLK2, EME1, and BIN2, or complements thereof, are furtherisolated from the biological sample, and/or purified, and/or amplifiedprior to analysis.

The prostate cancer can be any type of prostate cancer, including butnot limited to, adenocarcinoma, small cell prostate cancer, non-smallcell prostate cancer, neuroendocrine prostate cancer, or metastaticcastration resistant prostate cancer. Additionally, the prostate cancermay be biochemically recurrent or metastatic prostate cancer.

The expression levels of biomarker nucleic acids can be determined by avariety of methods including, but not limited to, microarray analysis,polymerase chain reaction (PCR), reverse transcriptase polymerase chainreaction (RT-PCR), a Northern blot, and serial analysis of geneexpression (SAGE).

In one aspect, the method further comprises prescribing and/oradministering the post-operative radiation therapy to the subject if thePORTOS indicates that the subject will benefit from the radiationtherapy, or prescribing and/or administering a cancer treatment otherthan the post-operative radiation therapy to the subject if the PORTOSindicates the subject will not benefit from the post-operative radiationtherapy.

In one aspect, the invention includes a method of predicting response topost-operative radiation therapy for prostate cancer, the methodcomprising: a) providing a biological sample comprising prostate cancercells from a subject; b) assaying a level of expression of a pluralityof genes in the biological sample, wherein said plurality of genescomprises one or more genes selected from the group consisting of DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11,CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2,PLK2, EME1, and BIN2; c) calculating a post-operative radiation therapyoutcome score (PORTOS) based on the levels of expression of theplurality of genes in the biological sample to determine whether or notthe subject is likely to benefit from the post-operative radiationtherapy. A PORTOS greater than 0 (i.e., high PORTOS) indicates that asubject will benefit from post-operative radiation therapy, whereas aPORTOS of less than or equal to 0 (i.e., low PORTOS) indicates that asubject will not benefit from post-operative radiation therapy.

In one aspect, the method further comprises prescribing and/oradministering the post-operative radiation therapy to the subject if thePORTOS indicates that the subject will benefit from the radiationtherapy, or prescribing and/or administering a cancer treatment otherthan the post-operative radiation therapy to the subject if the PORTOSindicates the subject will not benefit from the post-operative radiationtherapy.

In one aspect, the method further comprises prescribing and/oradministering the post-operative radiation therapy to the subject if thePORTOS indicates that the subject will benefit from the radiationtherapy, or prescribing and/or administering a cancer treatment otherthan the post-operative radiation therapy to the subject if the PORTOSindicates the subject will not benefit from the post-operative radiationtherapy.

In one embodiment, the plurality of genes comprises at least 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or24 genes selected from the group consisting of DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, andBIN2. In another embodiment, the plurality of genes comprises DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11,CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2,PLK2, EME1, and BIN2. In another embodiment, the plurality of genes isselected from DRAM1 and KRT14; DRAM1, KRT14 and PTPN22; DRAM1, KRT14,PTPN22 and ZMAT3; DRAM1, KRT14, PTPN22, ZMAT3 and ARHGAP15; DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15 and IL1B; DRAM1, KRT14, PTPN22, ZMAT3,ARHGAP15, IL1B and ANLN; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B,ANLN and RPS27A; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A and MUM1; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A, MUM1 and TOP2A; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B,ANLN, RPS27A, MUM1, TOP2A and GNG11; DRAM1, KRT14, PTPN22, ZMAT3,ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11 and CDKN3; DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11,CDKN3 and HCLS1; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1 and DTL; DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL and IL7R; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A,MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R and UBA7; DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3,HCLS1, DTL, IL7R, UBA7 and NEK1; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15,IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7,NEK1 and CDKN2AIP; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1,CDKN2AIP and APEX2; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1,CDKN2AIP, APEX2 and KIF23; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B,ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1,CDKN2AIP, APEX2, KIF23 and SULF2; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15,IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7,NEK1, CDKN2AIP, APEX2, KIF23, SULF2 and PLK2; DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2 and EME1; andDRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A,GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23,SULF2, PLK2, EME1 and BIN2.

In certain embodiments, the method is performed after the patientundergoes a radical prostatectomy. The method is preferably performedprior to treatment of the subject with radiation therapy to determine ifthe subject will benefit from radiation therapy or should beadministered some other anti-cancer treatment (e.g., chemotherapy,immunotherapy, hormonal therapy, biologic therapy, or a combinationthereof). The method may also be performed while the subject isundergoing radiation therapy to help evaluate whether continuedtreatment is likely to be efficacious.

The biological sample obtained from a patient is typically a biopsy ortumor sample, but can be any sample from bodily fluids or tissue of thepatient that contains cancerous cells. In certain embodiments, nucleicacids comprising sequences from genes selected from the group consistingof DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1,TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2,KIF23, SULF2, PLK2, EME1, and BIN2, or complements thereof, are furtherisolated from the biological sample, and/or purified, and/or amplifiedprior to analysis.

The prostate cancer can be any type of prostate cancer, including butnot limited to, adenocarcinoma, small cell prostate cancer, non-smallcell prostate cancer, neuroendocrine prostate cancer, or metastaticcastration resistant prostate cancer. Additionally, the prostate cancermay be biochemically recurrent or metastatic prostate cancer.

The expression levels of biomarker nucleic acids can be determined by avariety of methods including, but not limited to, microarray analysis,polymerase chain reaction (PCR), reverse transcriptase polymerase chainreaction (RT-PCR), a Northern blot, and serial analysis of geneexpression (SAGE).

In another aspect, the invention includes a method of treating a subjectfor prostate cancer, the method comprising: a) determining whether ornot the subject is likely to benefit from post-operative radiationtherapy according to a PORTOS as described herein; and b) administeringpost-operative radiation therapy to the subject if the PORTOS indicatesthat the subject will benefit from post-operative radiation therapy, oradministering a cancer treatment other than post-operative radiationtherapy to the subject if the PORTOS indicates that the subject will notbenefit from post-operative radiation therapy. Subjects, especiallythose identified as not likely to benefit from radiation therapy may beadministered other cancer treatments such as, but not limited to,chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or anycombination thereof.

In another aspect, the invention includes a method for determining atreatment for a subject who has prostate cancer, the method comprising:a) determining whether or not the subject is likely to benefit frompost-operative radiation therapy according to a PORTOS as describedherein; and b) prescribing radiation therapy to the subject if thePORTOS indicates that the subject will benefit from radiation therapy,or prescribing a cancer treatment other than radiation therapy to thesubject if the PORTOS indicates the subject will not benefit fromradiation therapy.

In another aspect, the invention includes a probe set for predictingresponse of a subject to post-operative radiation therapy for prostatecancer, the probe set comprising a plurality of probes for detecting aplurality of target nucleic acids, wherein the plurality of targetnucleic acids comprises one or more gene sequences, or complementsthereof, of genes selected from the group consisting of DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3,HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1,and BIN2. Probes may be detectably labeled to facilitate detection. Inone embodiment, the probe set comprises a plurality of probes fordetecting a plurality of target nucleic acids comprising gene sequences,or complements thereof, of the genes DRAM1, KRT14, PTPN22, ZMAT3,ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL,IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2.

In another aspect, the invention includes a system for predictingresponse of a subject to post-operative radiation therapy for prostatecancer, the system comprising: a) a probe set described herein; and b)an algorithm for generating a post-operative radiation therapy outcomescore (PORTOS) based on an expression level of the plurality of targetnucleic acids hybridized to the probes of the probe set in a biologicalsample from the subject.

In another aspect, the invention includes a kit for predicting responseof a subject to post-operative radiation therapy for prostate cancer,the kit comprising agents for measuring levels of expression of aplurality of genes, wherein the plurality of genes comprises one or moregenes selected from the group consisting of DRAM1, KRT14, PTPN22, ZMAT3,ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL,IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2.The kit may include one or more agents (e.g., hybridization probes, PCRprimers, or microarray) for measuring levels of expression of aplurality of genes, wherein said plurality of genes comprises one ormore genes selected from the group consisting of DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, andBIN2, a container for holding a biological sample comprising prostatecancer cells isolated from a human subject for testing, and printedinstructions for reacting the agents with the biological sample or aportion of the biological sample to determine whether or not the subjectis likely to benefit from radiation therapy. The agents may be packagedin separate containers. The kit may further comprise one or more controlreference samples or other reagents for measuring gene expression (e.g.,reagents for performing PCR, RT-PCR, microarray analysis, a Northernblot, SAGE, or an immunoassay). In one embodiment, the kit comprisesagents for measuring the levels of expression of the genes DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3,HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1,and BIN2. For example, the kit may comprise a probe set, as describedherein, for detecting a plurality of target nucleic acids, wherein theplurality of target nucleic acids comprises one or more gene sequences,or complements thereof, of genes selected from DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, andBIN2, or any combination thereof.

In another embodiment, the kit further comprises a system for predictingresponse of a subject to post-operative radiation therapy for prostatecancer, wherein the system comprises: a) a probe set comprising aplurality of probes for detecting a plurality of target nucleic acids,wherein the plurality of target nucleic acids comprises one or more genesequences, or complements thereof, of genes selected from DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3,HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1,and BIN2, or any combination thereof; and b) an algorithm for generatinga post-operative radiation therapy outcome score (PORTOS) based on anexpression level of the plurality of target nucleic acids hybridized tothe plurality of probes in a biological sample from the subject.

In another aspect, the invention includes a computer implemented methodfor predicting response of a patient to post-operative radiation therapyfor prostate cancer, the computer performing steps comprising: a)receiving inputted patient data comprising values for levels ofexpression of a plurality of genes, wherein said plurality of genescomprises one or more genes selected from the group consisting of DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11,CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2,PLK2, EME1, and BIN2 in a biological sample comprising prostate cancercells from the patient; b) calculating a post-operative radiationtherapy outcome score (PORTOS) based on the levels of expression of theplurality of genes to determine whether or not the patient is likely tobenefit from the radiation therapy, wherein a PORTOS greater than 0indicates that the patient will benefit from the radiation therapy and aPORTOS less than or equal to 0 indicates that the patient will notbenefit from the radiation therapy; and c) displaying informationregarding whether or not the patient is likely to benefit from thepost-operative radiation therapy. In one embodiment, the plurality ofgenes comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, or 24 genes selected from the groupconsisting of DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A,MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP,APEX2, KIF23, SULF2, PLK2, EME1, and BIN2. In another embodiment, theplurality of genes comprises DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15,IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7,NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2. In anotherembodiment, the plurality of genes is selected from DRAM1 and KRT14;DRAM1, KRT14 and PTPN22; DRAM1, KRT14, PTPN22 and ZMAT3; DRAM1, KRT14,PTPN22, ZMAT3 and ARHGAP15; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15 andIL1B; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B and ANLN; DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN and RPS27A; DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A and MUM1; DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1 and TOP2A; DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A andGNG11; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1,TOP2A, GNG11 and CDKN3; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B,ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3 and HCLS1; DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1and DTL; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A,MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL and IL7R; DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL, IL7R and UBA7; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7 and NEK1;DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A,GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1 and CDKN2AIP; DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3,HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP and APEX2; DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2 and KIF23; DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23 and SULF2; DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3,HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2 and PLK2;DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A,GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23,SULF2, PLK2 and EME1; and DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B,ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1,CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1 and BIN2.

The significance of the expression levels of one or more biomarker genesmay be evaluated using, for example, a T-test, P-value, KS (KolmogorovSmirnov) P-value, accuracy, accuracy P-value, positive predictive value(PPV), negative predictive value (NPV), sensitivity, specificity, AUC,AUC P-value (Auc.pvalue), Wilcoxon Test P-value, Median Fold Difference(MFD), Kaplan Meier (KM) curves, survival AUC (survAUC), Kaplan MeierP-value (KM P-value), Univariable Analysis Odds Ratio P-value(uvaORPval), multivariable analysis Odds Ratio P-value (mvaORPval),Univariable Analysis Hazard Ratio P-value (uvaHRPval) and MultivariableAnalysis Hazard Ratio P-value (mvaHRPval). The significance of theexpression level of the one or more targets may be based on two or moremetrics selected from the group comprising AUC, AUC P-value(Auc.pvalue), Wilcoxon Test P-value, Median Fold Difference (MFD),Kaplan Meier (KM) curves, survival AUC (survAUC), Univariable AnalysisOdds Ratio P-value (uvaORPval), multivariable analysis Odds RatioP-value (mvaORPval), Kaplan Meier P-value (KM P-value), UnivariableAnalysis Hazard Ratio P-value (uvaHRPval) or Multivariable AnalysisHazard Ratio P-value (mvaHRPval).

These and other embodiments of the subject invention will readily occurto those of skill in the art in view of the disclosure herein.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference in their entiretiesto the same extent as if each individual publication, patent, or patentapplication was specifically and individually indicated to beincorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1D show interaction and bar plots of 10-year metastasis ratesin a training and validation cohorts when comparing low and high PORTOS.In the line plots: Gray = treated with RT, black = not treated with RT.In the bar plots: Gray = low PORTOS, Black = high PORTOS, error bars =standard error.

FIGS. 2A-2D show cumulative incidence curves in the training andvalidation cohorts separating low and high PORTOS scores.

DETAILED DESCRIPTION OF THE INVENTION

The practice of the present invention will employ, unless otherwiseindicated, conventional methods of medicine, biochemistry, molecularbiology and recombinant DNA techniques, within the skill of the art.Such techniques are explained fully in the literature. See, e.g.,Radiotherapy in Prostate Cancer: Innovative Techniques and CurrentControversies (Medical Radiology, H. Geinitz, M. Roach III, and N. vanAs eds., Springer, 2015); Prostate Cancer: Science and Clinical Practice(J.H. Mydlo and C.J. Godec eds., Academic Press, 2^(nd) edition, 2015);Prostate Cancer: Biochemistry, Molecular Biology and Genetics (ProteinReviews 16, D.J. Tindall ed., Springer, 2013); A.L. Lehninger,Biochemistry (Worth Publishers, Inc., current addition); Sambrook, etal., Molecular Cloning: A Laboratory Manual (3^(rd) Edition, 2001); andMethods In Enzymology (S. Colowick and N. Kaplan eds., Academic Press,Inc.).

I. Definitions

In describing the present invention, the following terms will beemployed, and are intended to be defined as indicated below.

It must be noted that, as used in this specification and the appendedclaims, the singular forms “a,” “an” and “the” include plural referentsunless the content clearly dictates otherwise. Thus, for example,reference to “a nucleic acid” includes a mixture of two or more suchnucleic acids, and the like.

The term “survival” as used herein means the time from the start ofcancer treatment (e.g., radiation therapy) to the time of death.

The terms “tumor,” “cancer” and “neoplasia” are used interchangeably andrefer to a cell or population of cells whose growth, proliferation orsurvival is greater than growth, proliferation or survival of a normalcounterpart cell, e.g. a cell proliferative, hyperproliferative ordifferentiative disorder. Typically, the growth is uncontrolled. Theterm “malignancy” refers to invasion of nearby tissue. The term“metastasis” or a secondary, recurring or recurrent tumor, cancer orneoplasia refers to spread or dissemination of a tumor, cancer orneoplasia to other sites, locations or regions within the subject, inwhich the sites, locations or regions are distinct from the primarytumor or cancer. Neoplasia, tumors and cancers include benign,malignant, metastatic and non-metastatic types, and include any stage(I, II, III, IV or V) or grade (G1, G2, G3, etc.) of neoplasia, tumor,or cancer, or a neoplasia, tumor, cancer or metastasis that isprogressing, worsening, stabilized or in remission. In particular, theterms “tumor,” “cancer” and “neoplasia” include carcinomas, such assquamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma,anaplastic carcinoma, large cell carcinoma, and small cell carcinoma.

The term “derived from” is used herein to identify the original sourceof a molecule but is not meant to limit the method by which the moleculeis made which can be, for example, by chemical synthesis or recombinantmeans.

“Recombinant” as used herein to describe a nucleic acid molecule means apolynucleotide of genomic, cDNA, viral, semisynthetic, or syntheticorigin which, by virtue of its origin or manipulation is not associatedwith all or a portion of the polynucleotide with which it is associatedin nature. The term “recombinant” as used with respect to a protein orpolypeptide means a polypeptide produced by expression of a recombinantpolynucleotide. In general, the gene of interest is cloned and thenexpressed in transformed organisms, as described further below. The hostorganism expresses the foreign gene to produce the protein underexpression conditions.

“Substantially purified” generally refers to isolation of a substance(compound, polynucleotide, oligonucleotide, protein, or polypeptide)such that the substance comprises the majority percent of the sample inwhich it resides. Typically in a sample, a substantially purifiedcomponent comprises 50%, preferably 80%-85%, more preferably 90-95% ofthe sample. Techniques for purifying polynucleotides oligonucleotidesand polypeptides of interest are well-known in the art and include, forexample, ion-exchange chromatography, affinity chromatography andsedimentation according to density.

By “isolated” is meant, when referring to a polypeptide, that theindicated molecule is separate and discrete from the whole organism withwhich the molecule is found in nature or is present in the substantialabsence of other biological macro molecules of the same type. The term“isolated” with respect to a polynucleotide or oligonucleotide is anucleic acid molecule devoid, in whole or part, of sequences normallyassociated with it in nature; or a sequence, as it exists in nature, buthaving heterologous sequences in association therewith; or a moleculedisassociated from the chromosome.

The terms “polynucleotide,” “oligonucleotide,” “nucleic acid” and“nucleic acid molecule” are used herein to include a polymeric form ofnucleotides of any length, either ribonucleotides ordeoxyribonucleotides. This term refers only to the primary structure ofthe molecule. Thus, the term includes triple-, double- andsingle-stranded DNA, as well as triple-, double- and single-strandedRNA. It also includes modifications, such as by methylation and/or bycapping, and unmodified forms of the polynucleotide. More particularly,the terms “polynucleotide,” “oligonucleotide,” “nucleic acid” and“nucleic acid molecule” include polydeoxyribonucleotides (containing2-deoxy-D-ribose), polyribonucleotides (containing D-ribose), any othertype of polynucleotide which is an N- or C-glycoside of a purine orpyrimidine base, and other polymers containing nonnucleotidic backbones,for example, polyamide (e.g., peptide nucleic acids (PNAs)) andpolymorpholino (commercially available from the Anti-Virals, Inc.,Corvallis, Oregon, as Neugene) polymers, and other syntheticsequence-specific nucleic acid polymers providing that the polymerscontain nucleobases in a configuration which allows for base pairing andbase stacking, such as is found in DNA and RNA. There is no intendeddistinction in length between the terms “polynucleotide,”“oligonucleotide,” “nucleic acid” and “nucleic acid molecule,” and theseterms will be used interchangeably. Thus, these terms include, forexample, 3′-deoxy-2′,5′-DNA, oligodeoxyribonucleotide N3′ P5′phosphoramidates, 2′-O-alkyl-substituted RNA, double- andsingle-stranded DNA, as well as double- and single-stranded RNA, DNA:RNAhybrids, and hybrids between PNAs and DNA or RNA, and also include knowntypes of modifications, for example, labels which are known in the art,methylation, “caps,” substitution of one or more of the naturallyoccurring nucleotides with an analog, internucleotide modifications suchas, for example, those with uncharged linkages (e.g., methylphosphonates, phosphotriesters, phosphoramidates, carbamates, etc.),with negatively charged linkages (e.g., phosphorothioates,phosphorodithioates, etc.), and with positively charged linkages (e.g.,aminoalklyphosphoramidates, aminoalkylphosphotriesters), thosecontaining pendant moieties, such as, for example, proteins (includingnucleases, toxins, antibodies, signal peptides, poly-L-lysine, etc.),those with intercalators (e.g., acridine, psoralen, etc.), thosecontaining chelators (e.g., metals, radioactive metals, boron, oxidativemetals, etc.), those containing alkylators, those with modified linkages(e.g., alpha anomeric nucleic acids, etc.), as well as unmodified formsof the polynucleotide or oligonucleotide. The term also includes lockednucleic acids (e.g., comprising a ribonucleotide that has a methylenebridge between the 2′-oxygen atom and the 4′-carbon atom). See, forexample, Kurreck et al. (2002) Nucleic Acids Res. 30: 1911-1918; Elayadiet al. (2001) Curr. Opinion Invest. Drugs 2: 558-561; Orum et al. (2001)Curr. Opinion Mol. Ther. 3: 239-243; Koshkin et al. (1998) Tetrahedron54: 3607-3630; Obika et al. (1998) Tetrahedron Lett. 39: 5401-5404.

As used herein, the term “probe” or “oligonucleotide probe” refers to apolynucleotide, as defined above, that contains a nucleic acid sequencecomplementary to a nucleic acid sequence present in the target nucleicacid analyte (e.g., biomarker). The polynucleotide regions of probes maybe composed of DNA, and/or RNA, and/or synthetic nucleotide analogs.Probes may be labeled in order to detect the target sequence. Such alabel may be present at the 5′ end, at the 3′ end, at both the 5′ and 3′ends, and/or internally.

The term “primer” or “oligonucleotide primer” as used herein, refers toan oligonucleotide that hybridizes to the template strand of a nucleicacid and initiates synthesis of a nucleic acid strand complementary tothe template strand when placed under conditions in which synthesis of aprimer extension product is induced, i.e., in the presence ofnucleotides and a polymerization inducing agent such as a DNA or RNApolymerase and at suitable temperature, pH, metal concentration, andsalt concentration. The primer is preferably single stranded for maximumefficiency in amplification, but may alternatively be double stranded.If double stranded, the primer can first be treated to separate itsstrands before being used to prepare extension products. Thisdenaturation step is typically effected by heat, but may alternativelybe carried out using alkali, followed by neutralization. Thus, a“primer” is complementary to a template, and complexes by hydrogenbonding or hybridization with the template to give a primer/templatecomplex for initiation of synthesis by a polymerase, which is extendedby the addition of covalently bonded bases linked at its 3′ endcomplementary to the template in the process of DNA or RNA synthesis.Typically, nucleic acids are amplified using at least one set ofoligonucleotide primers comprising at least one forward primer and atleast one reverse primer capable of hybridizing to regions of a nucleicacid flanking the portion of the nucleic acid to be amplified.

The term “amplicon” refers to the amplified nucleic acid product of aPCR reaction or other nucleic acid amplification process (e.g., ligasechain reaction (LGR), nucleic acid sequence based amplification (NASBA),transcription-mediated amplification (TMA), Q-beta amplification, stranddisplacement amplification, or target mediated amplification). Ampliconsmay comprise RNA or DNA depending on the technique used foramplification.

The terms “hybridize” and “hybridization” refer to the formation ofcomplexes between nucleotide sequences which are sufficientlycomplementary to form complexes via Watson-Crick base pairing.

It will be appreciated that the hybridizing sequences need not haveperfect complementarity to provide stable hybrids. In many situations,stable hybrids will form where fewer than about 10% of the bases aremismatches, ignoring loops of four or more nucleotides. Accordingly, asused herein the term “complementary” refers to an oligonucleotide thatforms a stable duplex with its “complement” under assay conditions,generally where there is about 90% or greater homology.

The terms “selectively detects” or “selectively detecting” refer to thedetection of nucleic acids using oligonucleotides, e.g., primers orprobes that are capable of detecting a particular nucleic acid, forexample, by amplifying and/or binding to at least a portion of thebiomarker nucleic acid, but do not amplify and/or bind to sequences fromother nucleic acids under appropriate hybridization conditions.

As used herein, the terms “label” and “detectable label” refer to amolecule capable of detection, including, but not limited to,radioactive isotopes, fluorescers, chemiluminescers, chromophores,enzymes, enzyme substrates, enzyme cofactors, enzyme inhibitors,semiconductor nanoparticles, dyes, metal ions, metal sols, ligands(e.g., biotin, streptavidin or haptens) and the like. The term“fluorescer” refers to a substance or a portion thereof which is capableof exhibiting fluorescence in the detectable range. Particular examplesof labels which may be used in the practice of the invention include,but are not limited to, a SYBR dye such as SYBR green and SYBR gold, aCAL Fluor dye such as CAL Fluor Gold 540, CAL Fluor Orange 560, CALFluor Red 590, CAL Fluor Red 610, and CAL Fluor Red 635, a Quasar dyesuch as Quasar 570, Quasar 670, and Quasar 705, an Alexa Fluor such asAlexa Fluor 350, Alexa Fluor 488, Alexa Fluor 546, Alexa Fluor 555,Alexa Fluor 594, Alexa Fluor 647, and Alexa Fluor 784, a cyanine dyesuch as Cy3, Cy3.5, Cy5, Cy5.5, and Cy7, fluorescein, 2′, 4′, 5′,7′-tetrachloro-4-7-dichlorofluorescein (TET), carboxyfluorescein (FAM),6-carboxy-4′5′-dichloro-2′,7′-dimethoxyfluorescein (JOE),hexachlorofluorescein (HEX), rhodamine, carboxy-X-rhodamine (ROX),tetramethyl rhodamine (TAMRA), FITC, dansyl, umbelliferone, dimethylacridinium ester (DMAE), Texas red, luminol, quantum dots, NADPH,horseradish peroxidase (HRP), α-galactosidase, and β-galactosidase.

The terms “subject,” “individual,” and “patient,” are usedinterchangeably herein and refer to any mammalian subject, particularlyhumans. Other subjects may include cattle, dogs, cats, guinea pigs,rabbits, rats, mice, horses, and so on. In some cases, the methods ofthe invention find use in experimental animals, in veterinaryapplication, and in the development of animal models, including, but notlimited to, rodents including mice, rats, and hamsters; and primates.

II. Modes of Carrying Out the Invention

Before describing the present invention in detail, it is to beunderstood that this invention is not limited to particular formulationsor process parameters as such may, of course, vary. It is also to beunderstood that the terminology used herein is for the purpose ofdescribing particular embodiments of the invention only, and is notintended to be limiting.

Although a number of methods and materials similar or equivalent tothose described herein can be used in the practice of the presentinvention, the preferred materials and methods are described herein.

The present invention is based on the discovery of a genomic signaturethat is useful for identifying individuals who will be responsive topost-operative radiation therapy for treatment of prostate cancer. Inparticular, the invention relates to a genomic signature based onexpression levels of DNA damage repair genes that can be used toidentify individuals likely to benefit from post-operative radiationtherapy after a prostatectomy (see Examples).

In order to further an understanding of the invention, a more detaileddiscussion is provided below regarding the genomic signature and methodsof screening and treating subjects for prostate cancer.

A Genomic Signature for Predicting Response to Radiation Therapy

A genomic signature based on gene expression of DNA damage repair genescan be utilized to identify prostate cancer patients that maypotentially benefit from radiation therapy. Exemplary DNA damage repairgenes that display expression patterns that predict response toradiation therapy include DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B,ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1,CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2.

In one aspect the invention includes a method of predicting the responseof a subject to post-operative radiation therapy for prostate cancer.The method generally comprises: a) providing a biological samplecomprising prostate cancer cells from a subject; b) assaying a level ofexpression of a plurality of genes in the biological sample, wherein theplurality of genes comprises one or more genes selected from the groupconsisting of DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A,MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP,APEX2, KIF23, SULF2, PLK2, EME1, and BIN2; and c) predicting whether ornot the subject is likely to benefit from post-operative radiationtherapy based on the level of expression of the plurality of genes.

In certain embodiments, the plurality of genes comprises at least 2, atleast 3, at least 4, at least 5, at least 6, at least 7, at least 8, atleast 9, or at least 10 genes or more genes selected from the groupconsisting of DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A,MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP,APEX2, KIF23, SULF2, PLK2, EME1, and BIN2. In one embodiment, theplurality of genes comprises DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15,IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7,NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2. In anotherembodiment, the plurality of genes is selected from DRAM1 and KRT14;DRAM1, KRT14 and PTPN22; DRAM1, KRT14, PTPN22 and ZMAT3; DRAM1, KRT14,PTPN22, ZMAT3 and ARHGAP15; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15 andIL1B; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B and ANLN; DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN and RPS27A; DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A and MUM1; DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1 and TOP2A; DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A andGNG11; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1,TOP2A, GNG11 and CDKN3; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B,ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3 and HCLS1; DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1and DTL; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A,MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL and IL7R; DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL, IL7R and UBA7; DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7 and NEK1;DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A,GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1 and CDKN2AIP; DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3,HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP and APEX2; DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2 and KIF23; DRAM1, KRT14, PTPN22,ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1,DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23 and SULF2; DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3,HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2 and PLK2;DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A,GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23,SULF2, PLK2 and EME1; and DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B,ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1,CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1 and BIN2.

In another embodiment, a post-operative radiation therapy outcome score(PORTOS) is calculated based on the levels of expression of theplurality of genes in the biological sample to determine whether or notthe subject is likely to benefit from post-operative radiation therapy(see Examples). A PORTOS greater than 0 (i.e., high PORTOS) indicatesthat a subject will benefit from post-operative radiation therapy,whereas a PORTOS of less than or equal to 0 (i.e., low PORTOS) indicatesthat a subject will not benefit from post-operative radiation therapy.

In a further embodiment, the method is performed after the patientundergoes a radical prostatectomy. The method is preferably performedprior to treatment of the subject with radiation therapy to determine ifthe subject will benefit from radiation therapy or should beadministered some other anti-cancer treatment. The method may also beperformed while the subject is undergoing radiation therapy to helpevaluate whether continued treatment is likely to be efficacious.Subjects, especially those identified as not likely to benefit fromradiation therapy may be administered anti-cancer treatments other thanradiation therapy such as, but not limited to, surgery, chemotherapy,immunotherapy, hormonal therapy, biologic therapy, or any combinationthereof.

Targets

In some instances, assaying the expression level of a plurality of genescomprises detecting and/or quantifying a plurality of target analytes.In some embodiments, assaying the expression level of a plurality ofgenes comprises sequencing a plurality of target nucleic acids. In someembodiments, assaying the expression level of a plurality of biomarkergenes comprises amplifying a plurality of target nucleic acids. In someembodiments, assaying the expression level of a plurality of biomarkergenes comprises conducting a multiplexed reaction on a plurality oftarget analytes.

The methods disclosed herein often comprise assaying the expressionlevel of a plurality of targets. The plurality of targets may comprisecoding targets and/or non-coding targets of a protein-coding gene or anon-protein-coding gene. A protein-coding gene structure may comprise anexon and an intron. The exon may further comprise a coding sequence(CDS) and an untranslated region (UTR). The protein-coding gene may betranscribed to produce a pre-mRNA and the pre-mRNA may be processed toproduce a mature mRNA. The mature mRNA may be translated to produce aprotein.

A non-protein-coding gene structure may comprise an exon and intron.Usually, the exon region of a non-protein-coding gene primarily containsa UTR. The non-protein-coding gene may be transcribed to produce apre-mRNA and the pre-mRNA may be processed to produce a non-coding RNA(ncRNA).

A coding target may comprise a coding sequence of an exon. A non-codingtarget may comprise a UTR sequence of an exon, intron sequence,intergenic sequence, promoter sequence, non-coding transcript, CDSantisense, intronic antisense, UTR antisense, or non-coding transcriptantisense. A non-coding transcript may comprise a non-coding RNA(ncRNA).

In some instances, the plurality of targets comprises one or moretargets selected from Table 1 or Table 2. In some instances, theplurality of targets comprises at least about 2, at least about 3, atleast about 4, at least about 5, at least about 6, at least about 7, atleast about 8, at least about 9, at least about 10, at least about 15,at least about 20, or at least about 24 targets selected from Table 2.

In some instances, the plurality of targets comprises a coding target,non-coding target, or any combination thereof. In some instances, thecoding target comprises an exonic sequence. In other instances, thenon-coding target comprises a non-exonic or exonic sequence.Alternatively, a non-coding target comprises a UTR sequence, an intronicsequence, antisense, or a non-coding RNA transcript. In some instances,a non-coding target comprises sequences which partially overlap with aUTR sequence or an intronic sequence. A non-coding target also includesnon-exonic and/or exonic transcripts. Exonic sequences may compriseregions on a protein-coding gene, such as an exon, UTR, or a portionthereof. Non-exonic sequences may comprise regions on a protein-coding,non-protein-coding gene, or a portion thereof. For example, non-exonicsequences may comprise intronic regions, promoter regions, intergenicregions, a non-coding transcript, an exon anti-sense region, an intronicanti-sense region, UTR anti-sense region, non-coding transcriptanti-sense region, or a portion thereof. In other instances, theplurality of targets comprises a non-coding RNA transcript.

The plurality of targets may comprise one or more targets selected froma classifier disclosed herein. The classifier may be generated from oneor more models or algorithms. The one or more models or algorithms maybe a Cox proportional hazards model, Naive Bayes (NB), recursivePartitioning (Rpart), random forest (RF), support vector machine (SVM),k-nearest neighbor (KNN), high dimensional discriminate analysis (HDDA),or a combination thereof. The classifier may have an AUC of equal to orgreater than 0.60. The classifier may have an AUC of equal to or greaterthan 0.61. The classifier may have an AUC of equal to or greater than0.62. The classifier may have an AUC of equal to or greater than 0.63.The classifier may have an AUC of equal to or greater than 0.64. Theclassifier may have an AUC of equal to or greater than 0.65. Theclassifier may have an AUC of equal to or greater than 0.66. Theclassifier may have an AUC of equal to or greater than 0.67. Theclassifier may have an AUC of equal to or greater than 0.68. Theclassifier may have an AUC of equal to or greater than 0.69. Theclassifier may have an AUC of equal to or greater than 0.70. Theclassifier may have an AUC of equal to or greater than 0.75. Theclassifier may have an AUC of equal to or greater than 0.77. Theclassifier may have an AUC of equal to or greater than 0.78. Theclassifier may have an AUC of equal to or greater than 0.79. Theclassifier may have an AUC of equal to or greater than 0.80. The AUC maybe clinically significant based on its 95% confidence interval (CI). Theaccuracy of the classifier may be at least about 70%. The accuracy ofthe classifier may be at least about 73%. The accuracy of the classifiermay be at least about 75%. The accuracy of the classifier may be atleast about 77%. The accuracy of the classifier may be at least about80%. The accuracy of the classifier may be at least about 83%. Theaccuracy of the classifier may be at least about 84%. The accuracy ofthe classifier may be at least about 86%. The accuracy of the classifiermay be at least about 88%. The accuracy of the classifier may be atleast about 90%. The p-value of the classifier may be less than or equalto 0.05. The p-value of the classifier may be less than or equal to0.04. The p-value of the classifier may be less than or equal to 0.03.The p-value of the classifier may be less than or equal to 0.02. Thep-value of the classifier may be less than or equal to 0.01. The p-valueof the classifier may be less than or equal to 0.008. The p-value of theclassifier may be less than or equal to 0.006. The p-value of theclassifier may be less than or equal to 0.004. The p-value of theclassifier may be less than or equal to 0.002. The p-value of theclassifier may be less than or equal to 0.001. The p-value of theclassifier may be less than or equal to 0.0001.

The plurality of targets may comprise one or more targets selected froma Cox proportional hazards model. The plurality of targets may comprisetwo or more targets selected from a Cox proportional hazards model. Theplurality of targets may comprise three or more targets selected from aCox proportional hazards model. The plurality of targets may comprise 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,23, 24, 25, 30, 35, 40, 45, 50, or more targets selected from a Coxproportional hazards model. The Cox proportional hazards model may be aridge-penalized Cox model. Predictions from a Cox model can be describedin terms of a binary score (i.e., PORTOS) as discussed in the Examples.

TABLE 1 PORTOS Target Sequences SEQ ID NO. Affy Probeset ID GeneSequence 1 2378938 DTL AGATGCTGAAAAGAGAGTCGACTCC 2 2378938 DTLCGGTTAGTCTCTCGCACTGCAGTCA 3 2378938 DTL TCGACTCCGAAAAGGAGGCTGGGAC 42378938 DTL CCTGCAGCGAGCCTTCGGTTAGTCT 5 2378943 DTLGGAGGAAAACCTACATGGAAGAGAA 6 2378943 DTL AGTCACGTCACCATTACTACTTGTG 72378943 DTL CCTCTTTGTCCTCAGGGTCAAGGAG 8 2378943 DTLACTTGTGTGAAGAATACCTCTTTGT 9 2378944 DTL AACAAGCTAACATATTGTGTCTTAG 102378944 DTL ACCTTGTACATGATCGTCAACGGTT 11 2378944 DTLGAGGGTTATACCTTGTACATGATCG 12 2378944 DTL CGTCAACGGTTACTTCTTCCGAAAC 132378945 DTL GTGACCTTACGGCAGAAACTGGACC 14 2378945 DTLTACCTACCGAGTGACCTTACGGCAG 15 2378945 DTL ACCTTACGGCAGAAACTGGACCGGA 162378945 DTL ACCGAGTGACCTTACGGCAGAAACT 17 2378946 DTLTCGGAGTTCAGTCAACGGAAAAGAT 18 2378946 DTL TACGTTTCCAGTAGTTACGTCGGAG 192378946 DTL CCTGCATTTTCGACCACTCGACTAA 20 2378946 DTLACCTTGTACGTTTCCAGTAGTTACG 21 2378952 DTL CCGTTGTAATACCAGACCCTATGGT 222378952 DTL ACCGTTGTAATACCAGACCCTATGG 23 2378952 DTLTACCGTTGTAATACCAGACCCTATG 24 2378952 DTL CGTTGTAATACCAGACCCTATGGTC 252378953 DTL TTATGGAGTCTGTTCGTTTGGGGAA 26 2378953 DTLGTTCACTTAGTTTAGTCACCTCGAG 27 2378953 DTL ATATCCGTTCACTTAGTTTAGTCAC 282378953 DTL GTTTAGTCACCTCGAGTGTTATGGA 29 2378954 DTLCACCAGGAGAAAGTTCTGCTCTTAT 30 2378954 DTL CTTATGGAATCAGAGTCGTCCTCGA 312378954 DTL GGAGAAAGTTCTGCTCTTATGGAAT 32 2378954 DTLAAGGTCGTTTCACAATGACACCAGG 33 2378956 DTL AGATGAAATAAACGATTAACGTGTC 342378956 DTL AACGTGTCTGCTATTGTAGATGTAC 35 2378956 DTLCTATAAGTTCAGACTAAAACCTAAG 36 2378956 DTL GTAGATGTACAAATTATACTGACCC 372378957 DTL ATACATTTTAGGTCGGAATCAGGTC 38 2378957 DTLTCAAAAATCAGTCACCGAGTTCACT 39 2378957 DTL TTAGGTCGGAATCAGGTCTACTGGT 402378957 DTL ACCGATAAAAGTTACCTGTGGTCTT 41 2378959 DTLCGACCACAGGTAGACTGAAGTGTTT 42 2378959 DTL CCAGTAAGAGTTCTCCAGTGCAGAC 432378959 DTL GTGGGACCGTTGGAGGATGACACGA 44 2378959 DTLAGGTGTGGGACCGTTGGAGGATGAC 45 2378960 DTL TATTAATAGGTCAGTGTTCCGGAAT 462378960 DTL CTCAGTCGAAACAACCTTTAGACCT 47 2378960 DTLAGATATAGGACAAATAATCTGTTTT 48 2378960 DTL TGTTCCGGAATTCTGTGTGGACAAA 492378961 DTL GACCGCGAACTTATCTCCGAATCTC 50 2378961 DTLTTAGACCGCGAACTTATCTCCGAAT 51 2378961 DTL GCGAACTTATCTCCGAATCTCCTCT 522378961 DTL TTTTTAGACCGCGAACTTATCTCCG 53 2378963 DTLAGTCTTTCGACACCTTGCGATGGAG 54 2378963 DTL ACACGACGGAACGACCATTGGTCCT 552378963 DTL GGTGGACGAAGCCTCTGGTTCTAGT 56 2378963 DTLCAGAGGATAGTCAGGCATACGAAGT 57 2378968 DTL GTATGAAGGTATCTTTCAGGGTCCT 582378968 DTL GACGTGTATGAAGGTATCTTTCAGG 59 2378968 DTLAAGACACCAGGACTTGTGAGTTGTC 60 2378968 DTL AGGACTTGTGAGTTGTCTTAATATC 612378969 DTL ACCCACGGTTTCCAGTTGACATTAC 62 2378969 DTLGGGACTCCTGACACATCTGAAATAC 63 2378969 DTL AAGTCCACGTCAGTAGTCAAGAAAT 642378969 DTL GACCCATATTGTACAGAGTGAACCT 65 2378970 DTLAGATGTTTTTTCTTGATATCATCAG 66 2378970 DTL ACTCGAAAAACGTAATGGATCTTCG 672378970 DTL CGTAATGGATCTTCGTCAGATGTTT 68 2378970 DTLTCGAAAAACGTAATGGATCTTCGTC 69 2378972 DTL ACGTCAGACGTTTCCAGAAGTGTTT 702428797 PTPN22 AAAACGGATTTACCTCATATGGAAC 71 2428797 PTPN22CATGTTACATAGGTTGTCTGTGAGT 72 2428797 PTPN22 TAAGGGACTGTCAATAAAAACGGAT 732428797 PTPN22 CCCAACGTTATGTTTGACGAGAACT 74 2428798 PTPN22ATTCACGGTCAAAACGTAAAAGTAT 75 2428798 PTPN22 CGTTTTACGGTTATTCACGGTCAAA 762428798 PTPN22 TACTTCTATACGATTACACAATTAT 77 2428798 PTPN22ATTCACGAGATATACGTATTATAGT 78 2428799 PTPN22 TCCTTAGGTGGTGGTTGAACCTTAT 792428799 PTPN22 GTTCCTTAGGTGGTGGTTGAACCTT 80 2428799 PTPN22CTTAGGTGGTGGTTGAACCTTATAA 81 2428799 PTPN22 GGTTCCTTAGGTGGTGGTTGAACCT 822428800 PTPN22 AAGAACGGGTGGTTTGTTCGGACGT 83 2428800 PTPN22ACAAGTCAGTTTATTGAGGTCGAGT 84 2428800 PTPN22 AGTTTATTGAGGTCGAGTAAAGACT 852428800 PTPN22 GAACGGGTGGTTTGTTCGGACGTCT 86 2428801 PTPN22AGACTCAGACAGAAATCAGAAAGGG 87 2428801 PTPN22 CACTAGACTAGTTGTCAGTAGACTC 882428801 PTPN22 GAATTGTTAATATACACTAGACTAG 89 2428801 PTPN22CATTCGTGGATGTAAAACAATTGTA 90 2428806 PTPN22 ACTTCTGAGGACCTTTTTCAAAGTG 912428806 PTPN22 CTTCTGAGGACCTTTTTCAAAGTGT 92 2428806 PTPN22TCTGAGGACCTTTTTCAAAGTGTTC 93 2428806 PTPN22 GACTTCTGAGGACCTTTTTCAAAGT 942428809 PTPN22 ATAAAGACCGAAAGGGTCTGATCTT 95 2428809 PTPN22CAATTCAAATCTCATTAAGTGAAGT 96 2428809 PTPN22 AGTGAAGTCCTTCAATGAACCAAGG 972428809 PTPN22 CCAAGGGTATTATCGAAGGTCATAA 98 2428810 PTPN22ACATTTTGAGGCTTCAGGATTTAGT 99 2428811 PTPN22 CTTCCATTTTTAACCTTGTAGTGAC100 2428811 PTPN22 ACTACTGAGACACTATGAATCTGGT 101 2428811 PTPN22ACCCCACCTTGTAGACTTGGTTTCT 102 2428811 PTPN22 GAGACACTATGAATCTGGTTCGTTC103 2428814 PTPN22 GGTGAAGGACATACCTGTGGACTTA 104 2428814 PTPN22GGACTTAGTAAATAACACCAACTCC 105 2428814 PTPN22 GACATACCTGTGGACTTAGTAAATA106 2428814 PTPN22 AAGGACATACCTGTGGACTTAGTAA 107 2428815 PTPN22GGTACTGAGATCACGAGAACCACAT 108 2428815 PTPN22 TCTCGATCAAAACGTGGGACGATTT109 2428815 PTPN22 AGTAGTACCGGAGGTTCACCATGGT 110 2428815 PTPN22GGTTATCAACCCCTCGGAGAAGTCT 111 2428817 PTPN22 ATCTTGATAAATTCTCTGTCTACCT112 2428817 PTPN22 TCTCTGTCTACCTACAATAGTCTCT 113 2428817 PTPN22CCAGATGTTACGACATAATCTTGAT 114 2428817 PTPN22 ACTTGACCAGATGTTACGACATAAT115 2428818 PTPN22 GTCTCCGGAAGTAATCAAGTTTGCG 116 2428818 PTPN22CAAAAGTCAAACTAGGCCCTTTACG 117 2428818 PTPN22 CTCCGGAAGTAATCAAGTTTGCGTC118 2428818 PTPN22 GCCCTTTACGCCTGTGTCTCCGGAA 119 2428819 PTPN22ACGATAACTAATATGTACCTACAAC 120 2428819 PTPN22 AACTAATATGTACCTACAACGATTT121 2428819 PTPN22 ACACGATAACTAATATGTACCTACA 122 2428819 PTPN22GATAACTAATATGTACCTACAACGA 123 2428821 PTPN22 AGTAGACCCTACATGCAACAATGGT124 2428821 PTPN22 CTACTGTCACAAGGGTATACGTAAG 125 2428821 PTPN22ATATCTGGGATAAGAACTCGAGTAG 126 2428821 PTPN22 CTACATGGAAGTAGATATCTGGGAT127 2428823 PTPN22 GACTAATATATTAGTCCTGAGATTT 128 2428823 PTPN22CTAATATATTAGTCCTGAGATTTTC 129 2428823 PTPN22 ATATATTAGTCCTGAGATTTTCAAT130 2428823 PTPN22 ATATTAGTCCTGAGATTTTCAATTC 131 2428826 PTPN22ACAATACCGTACGTACCTCATACTT 132 2428826 PTPN22 ATACCGTACGTACCTCATACTTTAC133 2428826 PTPN22 TACGTACCTCATACTTTACCCTTTC 134 2428826 PTPN22AGTAACAATACCGTACGTACCTCAT 135 2428828 PTPN22 AGGGACTATTGGAGACTACTCCTAA136 2428828 PTPN22 TATCGGCCCATCTTGATAGGGACTA 137 2428828 PTPN22CTAATATCGGCCCATCTTGATAGGG 138 2428828 PTPN22 CTTGATAGGGACTATTGGAGACTAC139 2428829 PTPN22 GATAGGATGTTGACACCGACTCTTC 140 2428829 PTPN22CCGTCTGTTTTGGATAGGATGTTGA 141 2428829 PTPN22 GTTAGATGGTTCATGTTCCGTCTGT142 2428829 PTPN22 TTTCCGTTAGATGGTTCATGTTCCG 143 2428831 PTPN22TACCTGGTTTCTCTTTAAGACGTCT 144 2428831 PTPN22 TCTCCTCAAACGGTTACTTAAAGAC145 2428831 PTPN22 TTAATGATTTCTCCTCAAACGGTTA 146 2428831 PTPN22CTACTCCGGGTTTCGTTCTTTTAAT 147 2482925 RPS27A CGCAGACCATCTAACGACTAAGAGA148 2482925 RPS27A CGGGTTCCTCGCAGACCATCTAACG 149 2482925 RPS27ACCTCGCAGACCATCTAACGACTAAG 150 2482925 RPS27A CGTCCCTCCGCGATGTCCTCTCTTT151 2482926 RPS27A ATCGGTGCAACTAACATGCCCTTTT 152 2482926 RPS27AAAGAGAATCGGTGCAACTAACATGC 153 2482926 RPS27A GAGAATCGGTGCAACTAACATGCCC154 2482926 RPS27A GTGCAACTAACATGCCCTTTTCGGA 155 2482927 RPS27AAAAGCTTTCGTAAGGCTTCCGATTT 156 2482928 RPS27A AGCGACCCTGCCGTCAGTCCGTAAA157 2482928 RPS27A TGCTTCAAGTGCAGGATCAGACCGT 158 2482928 RPS27AAGACCGTGGCCCAACCTAACAGCGA 159 2482928 RPS27A CCTCTCCTCTTTGCTTCAAGTGCAG160 2482929 RPS27A AGAACACTAGGGACTGGATTGGACA 161 2482929 RPS27ACGACGAGAGCCCAATCGTGGGATAC 162 2482929 RPS27A AGACGTGAAGCCGACGAGAGCCCAA163 2482929 RPS27A CGTGGGATACCACGGAAGAGAACAC 164 2482931 RPS27AAAACGACTCGTTGCTGGATCTCCAC 165 2482931 RPS27A TGGACAGAGGAGAGCTCCCCAAGGT166 2482931 RPS27A TCGGTTCCAGGCTTATTCCAGGACT 167 2482931 RPS27ACAGAATCTGGTACTAAGGCTTAAAC 168 2482934 RPS27A TCACTCACCGCGTCAGTGACGTTGG169 2482934 RPS27A GTAAGCTTATCGTCATCTAAAAATC 170 2482934 RPS27ACCTTTTACCGTAAGCTTATCGTCAT 171 2482934 RPS27A CTCACTCACCGCGTCAGTGACGTTG172 2482935 RPS27A TACAGGGATATTTGACAGTCAATTC 173 2482935 RPS27ACATAGGGTACCACATTACATTACGT 174 2482935 RPS27A ACTCTTCGTGACGATATCAAGAGGG175 2482935 RPS27A GAGGGTAATACTTAAAACGTTCAAC 176 2482936 RPS27AACTTTCGAACGAAGTAAGAAGGTAA 177 2482936 RPS27A ACCTTAGTACTTTCGAACGAAGTAA178 2482936 RPS27A CGAACGAAGTAAGAAGGTAATTGTC 179 2482936 RPS27ATAGTACTTTCGAACGAAGTAAGAAG 180 2482937 RPS27A TCTTCTTCAGAATGTGGTGAGGGTT181 2482937 RPS27A CGTGTTCTCTTTCTTCCAATTCGAC 182 2482937 RPS27AACAACTCTGAAGCACCACCACGATT 183 2482937 RPS27A CAATTCGACCGACAGGACTTTATAA184 2482940 RPS27A CAAATACCGTTCAGTGAAACTGTCT 185 2482940 RPS27AACCGTTTTAATCAGCGGAAGCAGCT 186 2482940 RPS27A GCGGAAGCAGCTCTCACGGGAAGAC187 2482940 RPS27A ACAGACTGAATGACAAAGTTGTTTG 188 2482941 RPS27ACGATAGCGACACACTTACAACGGAG 189 2482941 RPS27A GTCCACGGTTGGTGAACATTTCCAG190 2482941 RPS27A GGTCACCAAGACATATGGACGGTCC 191 2482941 RPS27AAACGGAGACCCCTAATACACTGGGT 192 2482944 RPS27A AGTCGGGACAGCGACCAAGCCAAGT193 2482944 RPS27A CCATTAACAGTTTGATTTACTCAAG 194 2482944 RPS27ATTTACTCAAGACGACATCAAGGAAT 195 2482944 RPS27A GGAATTACACATTGGTTGTACGAAA196 2482946 RPS27A TGAACGCACTTAAACCTGTGAATAA 197 2482946 RPS27AATGGATCTAACCTTAGGAACTCCAC 198 2482946 RPS27A CGTGTCATGGATCTAACCTTAGGAA199 2482946 RPS27A CTCCACATAAAGTGAACGCACTTAA 200 2508612 ARHGAP15CAAAGTTATTGTCCAGTAACGGCTC 201 2508612 ARHGAP15 TGTCCGGATGAGAATGCTGTACACT202 2508612 ARHGAP15 TAATTGTCAATCCTCAACTACCGTC 203 2508612 ARHGAP15AATTCGTCGTAGGTTGTGTCCGGAT 204 2508620 ARHGAP15 TCCTTAGTAAGTGTCGTATAGAACT205 2508620 ARHGAP15 TTAGTAAGTGTCGTATAGAACTTTC 206 2508620 ARHGAP15TTCCTTAGTAAGTGTCGTATAGAAC 207 2508620 ARHGAP15 CCTTAGTAAGTGTCGTATAGAACTT208 2508622 ARHGAP15 ACCAACTTTTTCTTCCAATAGACGT 209 2508627 ARHGAP15ACTTAATTCGTTACTGTGTACTCCG 210 2508627 ARHGAP15 CTTAATTCGTTACTGTGTACTCCGA211 2508627 ARHGAP15 AACTTAATTCGTTACTGTGTACTCC 212 2508627 ARHGAP15AAACTTAATTCGTTACTGTGTACTC 213 2508628 ARHGAP15 TTCTTAGGTTCGTTGTCCGAGACAG214 2508628 ARHGAP15 TTTCTTAGGTTCGTTGTCCGAGACA 215 2508628 ARHGAP15AACAAGAAAGATCAGCTTCTTAACT 216 2508628 ARHGAP15 GAAAGATCAGCTTCTTAACTTAAAA217 2508633 ARHGAP15 CACGTAAGAACATGCACTCCACAAA 218 2508633 ARHGAP15CGACCACGTAAGAACATGCACTCCA 219 2508633 ARHGAP15 CCACGTAAGAACATGCACTCCACAA220 2508633 ARHGAP15 GACCACGTAAGAACATGCACTCCAC 221 2508634 ARHGAP15TTTGACCCGTGTTTGGTCTTTCACA 222 2508634 ARHGAP15 TTTTGACCCGTGTTTGGTCTTTCAC223 2508634 ARHGAP15 TCCTTTTTAGCTCGTCTTTCTTACA 224 2508674 ARHGAP15GTATCAAAGAAATGGACAGATAAAG 225 2508674 ARHGAP15 AACCTCATTAAGTCGAGATCGGGAT226 2508674 ARHGAP15 ATCTCTCGCCAAGTTTTACGAGGGT 227 2508674 ARHGAP15CGGGATGAGACTGAATTAGCAAGAT 228 2508675 ARHGAP15 AGTAGTATAACCTAACCAAGGTGCG229 2508675 ARHGAP15 GGTGCGATAGTTTTTACGTTAACTG 230 2508675 ARHGAP15CTCAAGGAAGATGTCAGTCTATAAC 231 2508675 ARHGAP15 GTGTTGTCATAGTCCTTTACTCAAG232 2508676 ARHGAP15 AGGAGATCGTGACTTAACGATTCAG 233 2508676 ARHGAP15AAGTTTTAGGTTTCTAGGAGATCGT 234 2508676 ARHGAP15 ACGATTCAGTGATGCTGTCACTATA235 2508676 ARHGAP15 GGTAGTTCTTTGGACCTTAATAAGT 236 2508677 ARHGAP15GAACGAGTAAAATTCAAACAGATTT 237 2508677 ARHGAP15 ACGAGTAAAATTCAAACAGATTTAC238 2508677 ARHGAP15 TGAACGAGTAAAATTCAAACAGATT 239 2508677 ARHGAP15CGAGTAAAATTCAAACAGATTTACG 240 2508678 ARHGAP15 CTAAACACGTGACCTCCCGTCAGAC241 2508678 ARHGAP15 AGTATGAGTACCTTCTAAGCATCGG 242 2508678 ARHGAP15ATCGGTAAAGGACCGGTCCCTAAAC 243 2508678 ARHGAP15 GTAGTAACAACCATTACGGAAAACT244 2508691 ARHGAP15 CTATGTTCGCTGTTTTTAGCTCAAT 245 2508691 ARHGAP15ACAAGTCTGACGTAGTGTCACGAAG 246 2508691 ARHGAP15 GCTGTTTTTAGCTCAATTTTCGTCT247 2508691 ARHGAP15 GTGTCACGAAGGCTATGTTCGCTGT 248 2508699 ARHGAP15AAACATTTCGTTACGTAACTTCGAC 249 2508699 ARHGAP15 ACGTGTTTCACACACTTGCACTTTT250 2508699 ARHGAP15 AGGTGTCAAGGCACCAAACATTTCG 251 2508699 ARHGAP15GTGTTTCACACACTTGCACTTTTAA 252 2508700 ARHGAP15 GGAGATGTGTTGGTTATGAGTTCAA253 2508700 ARHGAP15 ACGGTGGACTAAACAGACTCTTCGG 254 2508700 ARHGAP15GAGTTCAATCGTCACGGTGGACTAA 255 2508700 ARHGAP15 ACACGTCGTCAAGGGGGGTAATGAC256 2508706 ARHGAP15 CAGATCTACAACTACCTTATATAGC 257 2508706 ARHGAP15AGCTCAATCACCGTTAGACCGTTGT 258 2508706 ARHGAP15 ATCACCGTTAGACCGTTGTTATGTC259 2508706 ARHGAP15 CCTTATATAGCTCAATCACCGTTAG 260 2508711 ARHGAP15GGTCGGGAAGATAGTCTTGACCTAC 261 2508711 ARHGAP15 TCTTGACCTACCTCTGGACACCTGT262 2508711 ARHGAP15 CGGGAAGATAGTCTTGACCTACCTC 263 2508711 ARHGAP15AGACCTTATGGTCGGGAAGATAGTC 264 2508712 ARHGAP15 GACGTCTAAAAAGTGTCACCAGTAA265 2508712 ARHGAP15 TGGAGGTCTCGTTCGGTTATTAAAC 266 2508712 ARHGAP15TCACCAGTAAACTGGAGGTCTCGTT 267 2508712 ARHGAP15 CGACGTCTAAAAAGTGTCACCAGTA268 2508716 ARHGAP15 TCACCTAACCTCTGGTAGTGGAAAG 269 2508716 ARHGAP15TTCACCTAACCTCTGGTAGTGGAAA 270 2508716 ARHGAP15 ACCTAACCTCTGGTAGTGGAAAGAG271 2508716 ARHGAP15 CACCTAACCTCTGGTAGTGGAAAGA 272 2508717 ARHGAP15GGTTTCCTGGACACTAGAGTGGACG 273 2508717 ARHGAP15 TTAACCTGGTGATGTCCGAGACTGG274 2508717 ARHGAP15 ACTAGGGTTGGTTTGTATCACTTCC 275 2508717 ARHGAP15CCGAGACTGGTGTACATACTCTTCG 276 2508718 ARHGAP15 TCGAAGTCTCCAGGCTTAAACCGGT277 2508718 ARHGAP15 CTGAAGCCGGCAATTCTAAACGAAG 278 2508718 ARHGAP15GACCCTCTGAGCACGAGACATTCGT 279 2508718 ARHGAP15 TAGTACGACTGTATCTCCGTGGAAC280 2508719 ARHGAP15 TTGTAAGAGTTTTCCCGTGTCCGGG 281 2508719 ARHGAP15GACCAGCAGATAACACAGTCTTTCG 282 2508719 ARHGAP15 GACAGTTCATCAGTGTGCCTTTAAT283 2508719 ARHGAP15 GATTGATTAACTTGATGACCAGCAG 284 2508725 ARHGAP15CCTGTAGGTGCAACAGTGGCCTCGT 285 2508725 ARHGAP15 TCGACTTAAACCTGCTGTCGGTCAC286 2508725 ARHGAP15 ACTCGGCGAGAAGGGAATGTCAAAG 287 2508725 ARHGAP15GTGGCCTCGTGACTTCTACAAAAAG 288 2508741 ARHGAP15 GAGGCGGTTTAGCACTGTGGTACTT289 2508741 ARHGAP15 AGAACATGTTTTTGAGGGAGGCGGT 290 2508741 ARHGAP15TAACTTCGACATTTTAGAGAACATG 291 2508741 ARHGAP15 GCGGTTTAGCACTGTGGTACTTTCA292 2508742 ARHGAP15 ACGCATGTAGAGCATAAAAGGGAAC 293 2508742 ARHGAP15CATGGTGCACGACCCCGGTGTTTAT 294 2508742 ARHGAP15 GGGAACATCGACTTGATCCAGAAAG295 2508742 ARHGAP15 ACGAACAGTCTTGGTAGCGGACCTG 296 2508746 ARHGAP15GTCTTTTCGTGAGGTAAAAACGTCT 297 2508746 ARHGAP15 GAATTACGCCGTGTCAACCTGATCT298 2508746 ARHGAP15 AAGGTGAACTGGATGCATGAGATGT 299 2508746 ARHGAP15CCCTTACATTACTTCACGGTTTTTA 300 2508762 ARHGAP15 CTTTGTACCGCTAGGTGTACCAGAT301 2508762 ARHGAP15 CGAACCCCTAACATAAACCTGGATG 302 2508762 ARHGAP15ACCAGATGGTCTTGGTCTATCGACT 303 2508762 ARHGAP15 AACCTGGATGGGAAGACGCTCGACT304 2508763 ARHGAP15 ATTCTAGAAGCCGAGTCTCCTTCTG 305 2508763 ARHGAP15CATTCTAGAAGCCGAGTCTCCTTCT 306 2508763 ARHGAP15 TCTAGAAGCCGAGTCTCCTTCTGAC307 2508763 ARHGAP15 CTAGAAGCCGAGTCTCCTTCTGACT 308 2508764 ARHGAP15CGATGACTTATGCAAGTGTAGACAG 309 2508764 ARHGAP15 ATGTAAAGACATTTGTATAAAGACT310 2508764 ARHGAP15 GAAAGTTCGCTGTCTACGGAGTAAA 311 2508764 ARHGAP15AACACAAATTCAAGGTTTGTAAACT 312 2571511 IL1B GGTGTAAGACTACTCGTTGGCGAAG 3132571511 IL1B CCTGAGTTAGGGATCCCGACCGTCT 314 2571511 IL1BCGGGAAAACAACTCGGTCCGGAGAG 315 2571511 IL1B TTCTCCTAGAGGACAGGTAGTCGGT 3162571512 IL1B GGTTTCCGCCGGTCCTATATTGACT 317 2571512 IL1BTTGACTGAAGTGGTACGTTAAACAC 318 2571512 IL1B TTGTACGGGCAGAAGGACCCTCCCT 3192571512 IL1B GACCTTAAACTCAGACGGGTCAAGG 320 2571513 IL1BGCGGGGGTAGGGATCCTTTTCGACC 321 2571513 IL1B TTACGATACCTTACTTCGGGAAGAG 3222571513 IL1B ACTTACGATACCTTACTTCGGGAAG 323 2571513 IL1BAACTGTTAAAACGTAATTACATTTA 324 2571514 IL1B AGGACGCACAACTTTCTACTATTCG 3252571514 IL1B CCACAAGAGGTACAGGAAACATGTT 326 2571514 IL1BTAGACATGGACAGGACGCACAACTT 327 2571514 IL1B ACTATTCGGGTGAGATGTCGACCTC 3282571517 IL1B CGTGCTACGTGGACATGCTAGTGAC 329 2571517 IL1BATTGCTCCGAATACACGTGCTACGT 330 2571517 IL1B AGACCAGGTATACTTGACTTTCGAG 3312571517 IL1B AGTGACTTGACGTGCGAGGCCCTGA 332 2571518 IL1BGGAGGGACACCCGATCACAATACTG 333 2571518 IL1B CGACCTTGGGTACAGATTATCACAG 3342571518 IL1B GTCCCCGGAAAGTGAATGTAACAGT 335 2571518 IL1BATTCATCGAGACAACGAGCCGGTGT 336 2571519 IL1B GTCCGGCGCAGTCAACAACACCGGT 3372571519 IL1B CCTACCGCCGTAGGTCGATGCTTAG 338 2571519 IL1BCGCAGTCAACAACACCGGTACCTGT 339 2571519 IL1B ATGCTTAGAGGCTGGTGGTGATGTC 3402571520 IL1B CCTACTGAACAAGAAACTTCGACTA 341 2571520 IL1BCGTTACTCCTACTGAACAAGAAACT 342 2571520 IL1B TACTCCTACTGAACAAGAAACTTCG 3432571520 IL1B CTCCTACTGAACAAGAAACTTCGAC 344 2571522 IL1BTCATGGACTCGAGCGGTCACTTTAC 345 2571522 IL1B GCGGTCACTTTACTACCGAATAATG 3462571522 IL1B TGGACTCGAGCGGTCACTTTACTAC 347 2571522 IL1BTCGAGCGGTCACTTTACTACCGAAT 348 2571523 IL1B CAGTACCCCTTCAGTGAGTAAAAGA 3492571523 IL1B CGGCAGTACCCCTTCAGTGAGTAAA 350 2571523 IL1BACTTGCATCGGCAGTACCCCTTCAG 351 2571523 IL1B CTTTAGTGTGTACTTGCATCGGCAG 3522571524 IL1B TATAAGACCCTTACCTATGACGAAT 353 2571524 IL1BGAATACTGAGCCCTTTATAAGACCC 354 2571524 IL1B TTCCAATCACAGTTTCGGAGACGAG 3552571524 IL1B GTTGATCCACGATTCCCTCAGAGAG 356 2571525 IL1BCGGTATTTTTGTCGCTCCCTCTTTG 357 2571525 IL1B TGGAGAAGCTCCGTGTTCCGTGTTG 3582571525 IL1B TCTATGGTTTGGAGAAGCTCCGTGT 359 2571525 IL1BGGTTTGGAGAAGCTCCGTGTTCCGT 360 2674763 UBA7 ATCGAGTTACCTCGGGGCCTAGGGT 3612674763 UBA7 TACCTCGGGGCCTAGGGTTCGGGAC 362 2674763 UBA7ACAGTGGATCGAGTTACCTCGGGGC 363 2674763 UBA7 GTGGGACAGTGGATCGAGTTACCTC 3642674764 UBA7 CACTGCTGCTCCTGTGACGGAAGGG 365 2674764 UBA7CCGTCGCCCACAACCACGATCTCGA 366 2674764 UBA7 CGTCGCCCACAACCACGATCTCGAC 3672674766 UBA7 GCCTACCAGTGGACTTTTCGTCCGG 368 2674766 UBA7TACGCCGGCCTACCAGTGGACTTTT 369 2674766 UBA7 GTCGGGACGAGATACGCCGGCCTAC 3702674766 UBA7 TGGACTTTTCGTCCGGGTCGTGGAC 371 2674767 UBA7CACACGGGACAACGATGGGGTTGGG 372 2674767 UBA7 GACCACAGACTGGAAAGAGGAGATC 3732674767 UBA7 ACGGGACAACGATGGGGTTGGGGGT 374 2674767 UBA7TCGACCACAGACTGGAAAGAGGAGA 375 2674768 UBA7 CTGGCAGACTTCCATGGTCGACCCG 3762674768 UBA7 GTGGACTTCACCTGGAGAACCCTGG 377 2674768 UBA7CCTCAGCGACGACCGAGTAGAAGTC 378 2674768 UBA7 TCACCTGGAGAACCCTGGCAGACTT 3792674772 UBA7 GCCGTCGATCGGACTCTACAGTCTT 380 2674772 UBA7CTAAGGTGGCCAGTTGGCACGGGTC 381 2674772 UBA7 CTGAAACACCATCGCCGTCGATCGG 3822674772 UBA7 GACTCTACAGTCTTGATGCCCTAAG 383 2674773 UBA7TGTTTCGGGACCTTCAGACCTCACA 384 2674773 UBA7 GGGACTTCGGAGACTACAAACTCTT 3852674773 UBA7 GTCGTCTTCCTTGACTTGTTTCGGG 386 2674773 UBA7CCTCACACCCGGGAGGGGACTTCGG 387 2674775 UBA7 AGGAGATGCATGACCGTCGACGGTT 3882674775 UBA7 TAGATCTCGACCGAAGCCGAAGACG 389 2674775 UBA7GTCCTGACCTGACGTGAGTCCCTCG 390 2674775 UBA7 CGGTTGGACATACGGGTCTACGTAC 3912674776 UBA7 GGGAGTCTCGTCTCCATCCGTAAAG 392 2674776 UBA7GGTCTCTCTCGGTACGAACACGTAT 393 2674776 UBA7 ACCCTAAGACATCCCTCGAGGTTCT 3942674776 UBA7 CGTTTCCGTCCGTGAGTTTGTCTAG 395 2674777 UBA7CACGAACTCCTACCTTGAGGGAAGA 396 2674777 UBA7 CAGTCCAGGGTTTGTCACAGGGGTC 3972674777 UBA7 GGGAAGACCAGTCCAGGGTTTGTCA 398 2674777 UBA7CGAACTCCTACCTTGAGGGAAGACC 399 2674778 UBA7 TCGGGTCGTCGAAGATGAATGGATG 4002674778 UBA7 CGGGTCGTCGAAGATGAATGGATGG 401 2674778 UBA7GTCGTCGAAGATGAATGGATGGATC 402 2674778 UBA7 CACACCGATCCCCAACCCTGCGACC 4032674779 UBA7 CGACTCCGTGAAGGGTGGATTATTT 404 2674779 UBA7TTTGAGACGAAAGTAATACCGTAGT 405 2674779 UBA7 TACCGTAGTTTGTCGACGACTCCGT 4062674779 UBA7 ACGACTCCGTGAAGGGTGGATTATT 407 2674780 UBA7CACACCGCACCCGAGAACCGGTGAC 408 2674780 UBA7 ACACCGCACCCGAGAACCGGTGACC 4092674781 UBA7 AGGACTCTCACGCAGGTGTCTTGAC 410 2674781 UBA7CTCTCACGCAGGTGTCTTGACCGTT 411 2674781 UBA7 GACTCTCACGCAGGTGTCTTGACCG 4122674781 UBA7 CCCAGGACTCTCACGCAGGTGTCTT 413 2674782 UBA7CGGTGTCTGTGAGTGGAATGACTTC 414 2674782 UBA7 CCTACTCGGTGTCTGTGAGTGGAAT 4152674782 UBA7 TGTACCTACTCGGTGTCTGTGAGTG 416 2674782 UBA7ACTCGGTGTCTGTGAGTGGAATGAC 417 2674784 UBA7 AAACTTCTTGAGAAGGCTGACAGAC 4182674784 UBA7 GAAGGCTGACAGACGTCTCTGGTAG 419 2674784 UBA7ACTTCTTGAGAAGGCTGACAGACGT 420 2674784 UBA7 CTTGAGAAGGCTGACAGACGTCTCT 4212674785 UBA7 CCGCGATACACCGACGAGCAACGTG 422 2674785 UBA7AACGTGGGTGATAGACTTCGGTGAC 423 2674785 UBA7 GGATGGGACAGACATGGCACGCCAT 4242674785 UBA7 ATGGCACGCCATGAAGGGATCGTGT 425 2674786 UBA7GAACTGAAGCCTCCAGTCAGGGAAC 426 2674786 UBA7 ACTCACGAACTGAAGCCTCCAGTCA 4272674786 UBA7 AAGCCTCCAGTCAGGGAACGGGTGT 428 2674786 UBA7ACTGAAGCCTCCAGTCAGGGAACGG 429 2674787 UBA7 GAGGGCACACCTACCACACCGACGA 4302674787 UBA7 TCTGAATGTCCACTAGGGCGAGTGG 431 2674787 UBA7GGTGTCTCGTGTAGATACCCCTATT 432 2674787 UBA7 CACTAGGGCGAGTGGATGGGTGACC 4332674789 UBA7 CACTCACGACTGGGGAGAGGTGTGA 434 2674789 UBA7ACTCACGACTGGGGAGAGGTGTGAG 435 2674790 UBA7 TCGCGAGGTTAGAGTCGGCAGTCAA 4362674790 UBA7 ACGAGTTTCAGAAACGGGATCACCC 437 2674790 UBA7TACCTGGTGTATCTCGCGAGGTTAG 438 2674790 UBA7 CTGACAACAACTGTACCTGGTGTAT 4392674791 UBA7 TCCGTCGGCGATACTACCCGTTTAA 440 2674791 UBA7AGTCCTCTTTGACTCTGCGGTCGTG 441 2674791 UBA7 ACTACCCGTTTAACGTCACAAACCC 4422674791 UBA7 TTGACTCTGCGGTCGTGATGGAGGA 443 2674792 UBA7CGGGAGCTAACAGAAGGCCTTCTAC 444 2674792 UBA7 ATGAAACTACGGGAGCTAACAGAAG 4452674792 UBA7 AACAGAAGGCCTTCTACCCCTCGAG 446 2674792 UBA7CAGAAGGCCTTCTACCCCTCGAGGA 447 2674793 UBA7 TGGGTCGCGATCTCTCGTCGGGACC 4482674793 UBA7 GACCCACTTCGGAGGTCGGTCCTAG 449 2674793 UBA7CACAGTCTCCCGTGGGTCGCGATCT 450 2674793 UBA7 GGACCTCGGAAGTGGTTGGACCCAC 4512674794 UBA7 GAACTCGGGATACCACCGGTACGAC 452 2674794 UBA7TCAGCGGGATTCGTCACGTCCACAG 453 2674794 UBA7 GACCTTGGTGACTTCGCCTGTCTCC 4542674794 UBA7 TACTCCGGGATCACGCCTGTCAGCG 455 2674795 UBA7ATACGGGTGTCTCAGGATGGTTGTC 456 2674795 UBA7 GTCCGACCCCGATGATACGGGTGTC 4572674795 UBA7 ACCCCGATGATACGGGTGTCTCAGG 458 2674795 UBA7CGACCCCGATGATACGGGTGTCTCA 459 2674796 UBA7 ACGTAGTCCGGAAGACACGTGACGT 4602674796 UBA7 TAGTCCGGAAGACACGTGACGTGTT 461 2674796 UBA7GTAGTCCGGAAGACACGTGACGTGT 462 2674796 UBA7 CGTGGAGGTACCGGCCGGTGGGGTC 4632674797 UBA7 AAAGAGAGCCATGAACGCACCACCC 464 2674797 UBA7TGTTGAAAGAGAGCCATGAACGCAC 465 2674797 UBA7 CATGAACGCACCACCCCGATAGTGA 4662674797 UBA7 CTCTGTGTTGTTGAAAGAGAGCCAT 467 2674798 UBA7CCAACTCGAGTTGCTGACACTAGGG 468 2674798 UBA7 GAACCACTGAAAGAGCCCTTAACTC 4692674798 UBA7 CCCGGTTATGGGTGATGAAGGCACT 470 2674798 UBA7TTAACTCCCTTACCAACTCGAGTTG 471 2674799 UBA7 AAGACACTGAAACCACTCCTGAAGT 4722674799 UBA7 ACAAGACACTGAAACCACTCCTGAA 473 2674799 UBA7CAAGACACTGAAACCACTCCTGAAG 474 2674801 UBA7 TCCACCCGTGGAACACAGTATTCGT 4752674801 UBA7 GACTTCCACCCGTGGAACACAGTAT 476 2674801 UBA7CCGTGGAACACAGTATTCGTACCTC 477 2674801 UBA7 TCAAACGAAAGACCGCCGACTGTGG 4782674802 UBA7 ACGTGTGCCCACTGTAGTGACTCCT 479 2674802 UBA7GAGTTGTCTCGACAGGTCCAGCAGC 480 2674802 UBA7 GAGAGTTCTCGAGAACCGAGTCGAG 4812674802 UBA7 ACTCCTGGACGACAACCTGAAGGTC 482 2674804 UBA7ACCCGTCGGAGTGAGACGTACTAGG 483 2674804 UBA7 CGTCGGAGTGAGACGTACTAGGGGT 4842674804 UBA7 CCCGTCGGAGTGAGACGTACTAGGG 485 2674804 UBA7GGGTGGACGACCAGGCTGGACCGAC 486 2674805 UBA7 TACCTACGGGACCTGCGAAGCTTCG 4872674805 UBA7 TGCGAAGCTTCGATGACCTACTCCT 488 2674805 UBA7ACCTGCGAAGCTTCGATGACCTACT 489 2674805 UBA7 ACGGGACCTGCGAAGCTTCGATGAC 4902674806 UBA7 ATGACAGTGGCGGTGGATGTGTTTC 491 2674806 UBA7CGGTGGATGTGTTTCTGGGATAGAG 492 2674806 UBA7 ACAGTGGCGGTGGATGTGTTTCTGG 4932674806 UBA7 GTGGCGGTGGATGTGTTTCTGGGAT 494 2674807 UBA7GACACTGGTCGTCGCAGGGAATAAG 495 2674807 UBA7 CCAAGGACAAACGTGACCGATGTCG 4962674807 UBA7 TAAGCGAACCGGAACCAAGGACAAA 497 2674807 UBA7GTCGTCGCAGGGAATAAGCGAACCG 498 2691669 HCLS1 CAGGAGAGATAGGACCTACTCGAGT499 2691669 HCLS1 GGGCCCTTTCATGCAGATCTAACAC 500 2691669 HCLS1GAAAGACAAGTCAGGATTTTAAGCT 501 2691669 HCLS1 ACCAAACGGAGTAACACGATAAACG502 2691670 HCLS1 CCCCGTCTCTGTCGTACCCCTTCCT 503 2691670 HCLS1CAAGACCTGTCTGAAGGGAGAGGAC 504 2691670 HCLS1 AGTAATTCCCGAACCCCGTCTCTGT505 2691670 HCLS1 GGGAGAGGACGAAGTAATTCCCGAA 506 2691671 HCLS1GGGATAAGGACGACGTTTACAGATT 507 2691671 HCLS1 GACAGATGACGTTGACACTAAAGGG508 2691671 HCLS1 GGAGGGATAAGGACGACGTTTACAG 509 2691671 HCLS1AGGGATAAGGACGACGTTTACAGAT 510 2691672 HCLS1 CTGCATTAGTGACTGTAACTCTACC511 2691672 HCLS1 AGGAAACTAGGCCTGCTGCATTAGT 512 2691672 HCLS1CTTCACTACTCGAAAGGAAACTAGG 513 2691672 HCLS1 GGCCTGCTGCATTAGTGACTGTAAC514 2691674 HCLS1 TCGACACCGACATATACTAATGGTT 515 2691674 HCLS1AGTCGACACCGACATATACTAATGG 516 2691674 HCLS1 GTCGACACCGACATATACTAATGGT517 2691674 HCLS1 GACACCGACATATACTAATGGTTCC 518 2691675 HCLS1CCTCCACGAGCTCGGACTTCTAAGA 519 2691675 HCLS1 CCACGAGCTCGGACTTCTAAGAAGA520 2691675 HCLS1 CTGATACTCCTCCACGAGCTCGGAC 521 2691675 HCLS1CCCTGATACTCCTCCACGAGCTCGG 522 2691676 HCLS1 CAACTCCTCTACCTGTCCGTACTCG523 2691676 HCLS1 TCCTCTACCTGTCCGTACTCGTCCT 524 2691676 HCLS1TGCAACTCCTCTACCTGTCCGTACT 525 2691676 HCLS1 ACTCCTCTACCTGTCCGTACTCGTC526 2691677 HCLS1 CTCGGGCTCGGACTCTTACTGATAC 527 2691677 HCLS1CGGGCTCGGACTCTTACTGATACTC 528 2691677 HCLS1 CATGCTTCGTCTCGGACTCGGACTC529 2691677 HCLS1 TGCTTCGTCTCGGACTCGGACTCGG 530 2691678 HCLS1TCGAGACGGGGGATCCTGAGACCTT 531 2691679 HCLS1 GGAGGTAGTAGTCTCAGACTCGGAC532 2691679 HCLS1 TGGGTCACGGGAACGACGGGTAATC 533 2691679 HCLS1ACGGGTAATCCGTCTGAGAGGGCCT 534 2691679 HCLS1 ACCGGAGGTCAACCCTGAGGAGGTA535 2691680 HCLS1 TGACGGGTTCTTTTAGAGGAGTCTC 536 2691680 HCLS1GGTCACTATCGATACCTTCTCGGTC 537 2691680 HCLS1 TCACTATCGATACCTTCTCGGTCGT538 2691680 HCLS1 CTCGGTCGTCATGGCCGGGGTGACG 539 2691684 HCLS1AAACCACCGGTCATACCTTAGGTCT 540 2691684 HCLS1 AACCACCGGTCATACCTTAGGTCTT541 2691684 HCLS1 CCGAAACCACCGGTCATACCTTAGG 542 2691684 HCLS1CGAAACCACCGGTCATACCTTAGGT 543 2691686 HCLS1 ACCTCTTCCTATTTACCCTGTTTCG544 2691686 HCLS1 CTCTCTGCCTCTTTGTGCTCAGGGT 545 2691686 HCLS1TTCGTCGAGACCCTATACTGATGTT 546 2691686 HCLS1 GATGTTCCCTCTCTGCCTCTTTGTG547 2691692 HCLS1 GTCGTCAGCCGAAACTAATATTTCC 548 2691692 HCLS1TCGTCAGCCGAAACTAATATTTCCT 549 2691692 HCLS1 GTCAGCCGAAACTAATATTTCCTCT550 2691692 HCLS1 AGTCGTCAGCCGAAACTAATATTTC 551 2691693 HCLS1ACGAGACATCATAGGACACAGGTAT 552 2691693 HCLS1 TGGGTCAGTCACACAGTACATTTAG553 2691693 HCLS1 CGGACGGAAACGAATTAGTGGCTAA 554 2691693 HCLS1CGAGGTTTTGAGACGCCATTACAAC 555 2691694 HCLS1 AATTAATCCACCTGTACGTAGGAAT556 2691694 HCLS1 AACAATTAATCCACCTGTACGTAGG 557 2691694 HCLS1ACAATTAATCCACCTGTACGTAGGA 558 2691694 HCLS1 TTAATCCACCTGTACGTAGGAATTT559 2691695 HCLS1 TGTCGAGGAAGTGTCAATCGACTCT 560 2691695 HCLS1GTCGAGGAAGTGTCAATCGACTCTA 561 2691695 HCLS1 CTCCTGTCGAGGAAGTGTCAATCGA562 2691695 HCLS1 CCTGTCGAGGAAGTGTCAATCGACT 563 2691696 HCLS1CTTAGTAGATTCGAGAAGAAAACCG 564 2691696 HCLS1 ATGAGTACGGCAAATCCTTTTGTCT565 2691696 HCLS1 AATCGTAGTTAGATACTTCAGGTCT 566 2691696 HCLS1TATTAAGGAGTTCGGTGACCAAAAA 567 2691697 HCLS1 CGACACTCCTGGACTGTGGCAGTGT568 2691697 HCLS1 GGAACCACGGTTACAACCTTCGGTG 569 2691697 HCLS1TACCTCCGTGTACGAAGAAACAACT 570 2691697 HCLS1 CCTTCGGTGTACGACTCGACTTTCT571 2691698 HCLS1 CTGGTGAGAGAGAGGGTTGGTGGGT 572 2691698 HCLS1CATTCACTGGTGAGAGAGAGGGTTG 573 2691698 HCLS1 CACTGGTGAGAGAGAGGGTTGGTGG574 2691698 HCLS1 TTCACTGGTGAGAGAGAGGGTTGGT 575 2691699 HCLS1GTACTCATACAACGGCTCCACCTCT 576 2691699 HCLS1 CGAAACCCCCGTTCATGCCTCAACT577 2691699 HCLS1 CGTGAGAAGAGTCTGCCTACGACGG 578 2691699 HCLS1ATGCCTCAACTCTCCCTGTCCCGTC 579 2691700 HCLS1 GATACCTCCAGCCAAACCTCATCTT580 2691700 HCLS1 CTCAGTCCCGGGTTTCGTAGGGTAC 581 2691700 HCLS1CTCATCTTTCTCTGGCTTACCTGTT 582 2691700 HCLS1 ACTCCTTGTTTCATAGTCTCCTCGT583 2691701 HCLS1 TACTCGGAACCAGTACACCAAAGAA 584 2691701 HCLS1CGGAACCAGTACACCAAAGAAGGTC 585 2691701 HCLS1 CTCGGAACCAGTACACCAAAGAAGG586 2691701 HCLS1 TCGGAACCAGTACACCAAAGAAGGT 587 2691708 HCLS1GTTGACCTACTGTTATGGTGTAACA 588 2691708 HCLS1 CACCTACTGGTGTAACGTGTTCGTT589 2691708 HCLS1 AAAATTTTTCACAGTCACCTACTGG 590 2691708 HCLS1TCGTTGTATGACACTTTCGGACCGT 591 2691709 HCLS1 CACCCAGATAACCTAATTGACGGAG592 2691709 HCLS1 ATGGACACACAGTAACGTATAAAGG 593 2691709 HCLS1GGAAATCATTCCGTACTCTCTAAGT 594 2691709 HCLS1 AGATCTCAGACAAGGACACACATGG595 2691710 HCLS1 TCGGGTTTCTTTTGAGCCTCTGAAC 596 2691710 HCLS1TCTCGGGTTTCTTTTGAGCCTCTGA 597 2691711 HCLS1 TAGCTCCCCAGACCTGCGTGTCTTG598 2691711 HCLS1 TCGGTTCTGGTAGCTCCCCAGACCT 599 2691711 HCLS1CTGGTAGCTCCCCAGACCTGCGTGT 600 2691711 HCLS1 GTTCTGGTAGCTCCCCAGACCTGCG601 2691714 HCLS1 CTGTCCGGTACCGTCCGATGTGACT 602 2691714 HCLS1CCCCGTACGTGCTATGGACCATAGT 603 2691714 HCLS1 GTAGACCCGGTGAGACACTAGAAAC604 2691714 HCLS1 TGTCGGGAGTATGACCCTGATTAAC 605 2691715 HCLS1GGTACTACACAGACAAAGGCACCTC 606 2691715 HCLS1 GGGTCCCACTACTAACCCTGTGTCT607 2691715 HCLS1 AGACATCACCCGGTACTACACAGAC 608 2691715 HCLS1AACCCTGTGTCTAGGACTGAAACAC 609 2691717 HCLS1 TCGGCCCGCGAATCTTGTCTCCGAA610 2691717 HCLS1 CGAATCTTGTCTCCGAACGTGTCCA 611 2691717 HCLS1CGTCGTCGAGTCAAAGAGTGAGGCT 612 2691717 HCLS1 GTCAAAGAGTGAGGCTTCACCGTCG613 2706793 ZMAT3 CCCCGACGTCTTACTGTTTGCACAG 614 2706793 ZMAT3TGCGTAAAACACAAGGTCAAATTAT 615 2706793 ZMAT3 GACGAAAACAACTACCGAGTAAAAC616 2706793 ZMAT3 AGCCTCACGGTCAGTGACGAAACCT 617 2706794 ZMAT3ATCTTTGCGGGACGATCTGACTAAA 618 2706794 ZMAT3 GACCTCATACAGTCTAGGACGAAAT619 2706794 ZMAT3 TTCGGGCTGCGTCAACGATTTTTAG 620 2706794 ZMAT3ACAAGTGGACACCATAGGAACTGAC 621 2706795 ZMAT3 GATTTGACTCACACGGGACATTAGG622 2706795 ZMAT3 GGGTCACGGGAATTACCTACAATAC 623 2706795 ZMAT3GGGATGGTAACACTCGTCAATGACA 624 2706795 ZMAT3 ACGACCGGCGAACCAAGATACTAAT625 2706796 ZMAT3 ACTATCTAGTGAAACCGTAGACTAT 626 2706796 ZMAT3AACATTAAGCCGAAAGAACTTCTAT 627 2706796 ZMAT3 TCAAAGTGATAGAAGCAAAGGTCAT628 2706796 ZMAT3 TAGACTAAGAATGCCAAATGAATGT 629 2706797 ZMAT3GGGTGTCACCATGGTACTCTACAGT 630 2706797 ZMAT3 CGGACTGCCGAATCTTGAAACTGAT631 2706797 ZMAT3 ACAGTTGAACGGGACGAAACACCAG 632 2706797 ZMAT3CCAGTTACCACAACTCGGCGAGTAT 633 2706798 ZMAT3 CACAATGAGGTTCACCGGTCAAAAT634 2706798 ZMAT3 AGACTTGTCGCCATGTCCTTACTCT 635 2706798 ZMAT3CGTTCGTTGTATTCTCGTTCCACAG 636 2706798 ZMAT3 AATGACGAGTTACACATTACAACCT637 2706799 ZMAT3 AGGAATGAAGTTAGGGGCGAGAGCC 638 2706799 ZMAT3AATGAAGTTAGGGGCGAGAGCCGTC 639 2706799 ZMAT3 CAGGAATGAAGTTAGGGGCGAGAGC640 2706799 ZMAT3 GGAATGAAGTTAGGGGCGAGAGCCG 641 2706801 ZMAT3ACTACGGATTGTCCTCTTTATACAT 642 2706801 ZMAT3 CAAATTCTACTACGGATTGTCCTCT643 2706801 ZMAT3 AGTCTCGACCCAGTTGCCGCCCGGT 644 2706801 ZMAT3TTCTACTACGGATTGTCCTCTTTAT 645 2706802 ZMAT3 GTTCCCTTCTTAGTACGGTTCTCCG646 2706802 ZMAT3 ACACCGAGTCCGAGTGATAGTTCCC 647 2706802 ZMAT3CCGAGTGATAGTTCCCTTCTTAGTA 648 2706802 ZMAT3 TTCTTAGTACGGTTCTCCGACGCCG649 2706803 ZMAT3 GGCTCACTAGGACCGGTGCCTCTTA 650 2706803 ZMAT3TAGGACCGGTGCCTCTTACTAATGA 651 2706803 ZMAT3 GAAATTCGGTCCTCCGGCTCACTAG652 2706803 ZMAT3 CTCCGGCTCACTAGGACCGGTGCCT 653 2706804 ZMAT3CACCAGCTCGGACGTCGATGAGGTC 654 2706804 ZMAT3 TCGTTACACCAGCTCGGACGTCGAT655 2706804 ZMAT3 GTTACACCAGCTCGGACGTCGATGA 656 2706804 ZMAT3TACTCGTTACACCAGCTCGGACGTC 657 2706805 ZMAT3 CATTCTTTGAGGCTTTAATGATACG658 2706805 ZMAT3 CTTTGAGGCTTTAATGATACGTCGT 659 2706805 ZMAT3AGGCTTTAATGATACGTCGTTTATC 660 2706805 ZMAT3 TAGTACCATTCTTTGAGGCTTTAAT661 2706806 ZMAT3 CATGACGTTTGAGACGTTACAGTGG 662 2706806 ZMAT3GAGACGTTACAGTGGAACTTGAGAC 663 2706806 ZMAT3 TTACAGTGGAACTTGAGACGTGTCG664 2706806 ZMAT3 CGTTTGAGACGTTACAGTGGAACTT 665 2706807 ZMAT3GAAAACCCGTCCTCCGAAGGAACGG 666 2706807 ZMAT3 TACTAGGAGAACGTTGTGCGGCACG667 2706807 ZMAT3 AAGGAACGGAGAACGTCCCCTTCTT 668 2706807 ZMAT3CAGTCACCGGTGGTCCAGATGTCCT 669 2706808 ZMAT3 AGAGTAGTGGGTGACCTAATACGGG670 2706808 ZMAT3 AGTAGTGGGTGACCTAATACGGGGT 671 2706808 ZMAT3AAGAGTAGTGGGTGACCTAATACGG 672 2706808 ZMAT3 GTAGTGGGTGACCTAATACGGGGTC673 2706814 ZMAT3 GCACTACCGTAGGTATGGCCCAACT 674 2706814 ZMAT3TAGACACGCACGTCGACGGAACCGG 675 2706814 ZMAT3 CCCCTAAGGTAGGAAGCACTACCGT676 2706814 ZMAT3 GTCCACCTAGTAGACACGCACGTCG 677 2706815 ZMAT3GGAGGTGCACTGTCCCGAACGCGAC 678 2706815 ZMAT3 TCGCCAAGGAAAGGCTACGAGAAAG679 2706815 ZMAT3 GCACTGTCCCGAACGCGACGAAGAT 680 2706815 ZMAT3CCCTGATCGCCAAGGAAAGGCTACG 681 2706816 ZMAT3 GCCGCGCCTCTGACGGCCGCGCAGG682 2706816 ZMAT3 GCGCCTCTGACGGCCGCGCAGGGCC 683 2706817 ZMAT3CCAGCCCAACCTGACTGAAAACTGT 684 2706817 ZMAT3 CGCCGGCCGCCTCTTTCAACGAGGC685 2706817 ZMAT3 ACTGAAAACTGTCAGTCGGAAGCCG 686 2706817 ZMAT3AACTGTCAGTCGGAAGCCGACGCCT 687 2706819 ZMAT3 GTGTACGCGTCACCGCTGCGGCTCG688 2706819 ZMAT3 GTTACAAACCTAGGGTTACTGACCT 689 2706819 ZMAT3AATTGGCGGTTGGTCGTCCGATTCC 690 2706819 ZMAT3 CTACTTTCAACGTTTTCGAGACGGG691 2733718 BIN2 TTCATAGATATCTGTGTCTGTGAAC 692 2753897 CDKN2AIPAACAAACCAGAAATCCGGACGCCTC 693 2753897 CDKN2AIP CGCCTCCCCGCAATAGACCTCCCGG694 2753897 CDKN2AIP GAGACCCGCGACAACAAACCAGAAA 695 2753897 CDKN2AIPCGGCGCCCACGTCCGGCGTCACTGT 696 2753898 CDKN2AIP ACACAAGCGCCGGACGTCCGGGTTG697 2753899 CDKN2AIP GCTGCCGCTCTGACTGTTTGTGACC 698 2753899 CDKN2AIPGTGGCGGCCCTAAAAAACGAAGCGT 699 2753899 CDKN2AIP AAAAGGTACCGGACCCGCTTGGTGC700 2753899 CDKN2AIP GCGACGGAGGCGATCGTGCCTACTT 701 2753903 CDKN2AIPTTTTATGAATCATACCGACTTCCGT 702 2753903 CDKN2AIP AGTTTCACTGTCTACGAGGTTGGAT703 2753903 CDKN2AIP TGTTGTTCTCTACTTGACCAACGGT 704 2753903 CDKN2AIPCTGTCTACGAGGTTGGATATGTTGT 705 2753904 CDKN2AIP TTTTCTCCCTATAGCTCATCGTTAC706 2753904 CDKN2AIP CTTTTCTCCCTATAGCTCATCGTTA 707 2753905 CDKN2AIPCCATCTTCTCGGTAGGTTTTTTGCT 708 2753905 CDKN2AIP CATCTTCTCGGTAGGTTTTTTGCTC709 2753905 CDKN2AIP ATCTTCTCGGTAGGTTTTTTGCTCA 710 2753905 CDKN2AIPTCTTCTCGGTAGGTTTTTTGCTCAA 711 2753906 CDKN2AIP ACCTCTAGCTAGACAAAGGTCGGTT712 2753906 CDKN2AIP GGAGACGGTTCTGTCTTGCACGTAG 713 2753906 CDKN2AIPGACCGTAGAGGTCAGTCTTATCGAG 714 2753906 CDKN2AIP AAGTTGCACATATCCCAGCCGGTAG715 2753907 CDKN2AIP GGTTTGGATCAAGTCTCTGTCGAAG 716 2753907 CDKN2AIPCCGTGTAGGAATGACTGAGGGTTCT 717 2753907 CDKN2AIP CGTCTTCGAGGTCTATTTGTGCCAA718 2753907 CDKN2AIP CGAGTCTCTAGCTCCACGGGAACAA 719 2753908 CDKN2AIPTGAAGGAATCGTTCACACAGGGTCA 720 2753908 CDKN2AIP GTCAACCGAAGATTCTCATCAAGAG721 2753908 CDKN2AIP GAGGGTCTGGTCACCTAGAGACCAA 722 2753908 CDKN2AIPCAAGAGTCTGATCGTGGAGTGTCAA 723 2753909 CDKN2AIP GGAACTACTTCTTAGCTCCGGACAT724 2753909 CDKN2AIP GTTCAGACACATAAACCCGTGACCG 725 2753909 CDKN2AIPGTACCTCTCGAGGATTTACGTCGAT 726 2753909 CDKN2AIP CCACCGAAATCAGGGTTACACTTAG727 2753910 CDKN2AIP CCATACGTAATCGTCGTATAATCAT 728 2753910 CDKN2AIPACACATCAAGCCATCTCAGGATTTT 729 2753910 CDKN2AIP GATCAAGAGAAGTGTGTCATCGTCA730 2753910 CDKN2AIP CATAATTCAACAGATGGTACAAAAG 731 2753911 CDKN2AIPAGTGGTACTGAAACTGGCGACTTCT 732 2753911 CDKN2AIP GTGTCATAAACTTACAAACTTTCAG733 2753911 CDKN2AIP ACAACGGGCATTACAACTTGCACAG 734 2753911 CDKN2AIPACACTGATGATAATTGTCTAACTAA 735 2793222 NEK1 AGATTATAGGCTTTGATTTATGAAC 7362793222 NEK1 ATAAAGATTATAGGCTTTGATTTAT 737 2793222 NEK1TATAGGCTTTGATTTATGAACTAAA 738 2793222 NEK1 GATTATAGGCTTTGATTTATGAACT 7392793223 NEK1 CCTGGTCTTGGTCCTTATGATATAG 740 2793223 NEK1TCGTCCGACCAACCGTATTATACAT 741 2793223 NEK1 CCCGAGACAAATGTAGATATGTAAA 7422793223 NEK1 CCACAGATGTCAGGTCTACAAGAAG 743 2793227 NEK1AATCAGTACCGTCTACCTCGGATGG 744 2793227 NEK1 TACCGTCTACCTCGGATGGTTCTTC 7452793227 NEK1 AAGAAGTAAATCAGTACCGTCTACC 746 2793227 NEK1GTCGTAGAAATACGGTTCTAAGAAG 747 2793228 NEK1 CTTACGCTATCACAGAAATTGGTAA 7482793228 NEK1 CTTTTTAAGAAACTCCAAATACTCT 749 2793228 NEK1CACTTACACTTACGCTATCACAGAA 750 2793228 NEK1 AATTGGTAAATCTCCTTGACTCTGA 7512793229 NEK1 ACGTCCGGAGCTACCTTGTCAATGA 752 2793229 NEK1ATGAATCCCTTGTTGGACCACTTCT 753 2793229 NEK1 ACTTTCACGGGACTTGCTTCTTACC 7542793229 NEK1 TGTGTCTAAATGTTCTCGACGTCCG 755 2793230 NEK1CTCTACAAGCAGTTCTGTTAGAACT 756 2793231 NEK1 GACAAGTCTTGGGAATACCTACAAG 7572793231 NEK1 TGGGAATACCTACAAGGGTGGCATC 758 2793231 NEK1GAGAGTTTCGACAAGTCTTGGGAAT 759 2793231 NEK1 TCTTGGGAATACCTACAAGGGTGGC 7602793236 NEK1 CCTTGGTTACTAAGAGTCGTGAGAT 761 2793236 NEK1GTCAAGTCACAAGTGGTCTTCTTAG 762 2793236 NEK1 GGAACGACTAACCTGAAAGTTGACC 7632793236 NEK1 ACGTAAAGCTAGAGTGAGCGTAAAT 764 2793238 NEK1GTTCTCGGTTCACCTTGTTTGTTTC 765 2793238 NEK1 CTACTCTCGAACGGTACGTGATAAT 7662793238 NEK1 CTCTCGAACGGTACGTGATAATGAC 767 2793238 NEK1ACTCTCGAACGGTACGTGATAATGA 768 2793239 NEK1 CAACTAAGAGGACAACTCTGTTTTT 7692793239 NEK1 ATTTGGGTAGTCGATAACAACTAAG 770 2793239 NEK1ACAACTCTGTTTTTCAGGGCTCAAG 771 2793239 NEK1 GGGCTCAAGTCACTCCGTAGAGGTG 7722793240 NEK1 GCTGTCTAAGACAAGATTTCTATGA 773 2793240 NEK1TTAATCCAGGATTACCTAGAGGTTC 774 2793240 NEK1 CCCTTTTCAGGCTGTCTAAGACAAG 7752793240 NEK1 CCTCTTCGACTTGATGTTGAAGTCT 776 2793241 NEK1GGAGACCTACTCAATTGTGATCTAT 777 2793241 NEK1 ATCTATGTAGGAAGAGATGTTGACT 7782793241 NEK1 ACTCAATTGTGATCTATGTAGGAAG 779 2793241 NEK1CAGTTGAACACTAAGGAGACCTACT 780 2793242 NEK1 CTTTATGAAGCATCTAATTTACTTT 7812793242 NEK1 TAGACTAGCGTTCTTCACCCTCCGT 782 2793242 NEK1TCGCTCTTTATGAAGCATCTAATTT 783 2793242 NEK1 TTTAGTCAAAGTAGACTAGCGTTCT 7842793243 NEK1 ACTATGGGCCCTTTGAAGTCTTCTC 785 2793243 NEK1TGACTATGGGCCCTTTGAAGTCTTC 786 2793243 NEK1 GGGCCCTTTGAAGTCTTCTCTACGT 7872793243 NEK1 CCTTTGAAGTCTTCTCTACGTTTTC 788 2793244 NEK1TTCGTTGTCTACTCTAGACAATAAA 789 2793244 NEK1 TCGTTGTCTACTCTAGACAATAAAG 7902793244 NEK1 GAGGTAGTTTCGTTGTCTACTCTAG 791 2793244 NEK1GGTAGTTTCGTTGTCTACTCTAGAC 792 2793246 NEK1 CGACGACATGATTTTCTTGTTGATC 7932793246 NEK1 GCACGACGACATGATTTTCTTGTTG 794 2793246 NEK1ACGTGCACGACGACATGATTTTCTT 795 2793246 NEK1 TTACGTGCACGACGACATGATTTTC 7962793247 NEK1 CTCCGCGTTTTTTTAGCTTAGTGAC 797 2793247 NEK1ACTGTACTCCGCGTTTTTTTAGCTT 798 2793247 NEK1 CGCGTTTTTTTAGCTTAGTGACTTC 7992793247 NEK1 GTACTCCGCGTTTTTTTAGCTTAGT 800 2793249 NEK1CGTCGATACATACCTCCGTCCGGGT 801 2793249 NEK1 TGGACCGTCGATACATACCTCCGTC 8022793249 NEK1 TACATACCTCCGTCCGGGTCGAGAA 803 2793249 NEK1ACGTTTTGGACCGTCGATACATACC 804 2793255 NEK1 TACGGGTCGGTCTTACCTACATGAT 8052793255 NEK1 CCACGGAGGCATATAGAAGTATCAA 806 2793255 NEK1AATCTCGCTAAACCCCAAGTGTCGT 807 2793255 NEK1 GTGACCGAAAAGAGTGAATGATTAT 8082793256 NEK1 TATCGAATCATGGATGTGAAACACC 809 2793256 NEK1AAGACTCCACGTTTAAACCGGGAAC 810 2793256 NEK1 GAACCCATGTTATTAAAAGACTCCA 8112793256 NEK1 AACCGGGAACTAATGAGACTTTCGT 812 2793258 NEK1AATGGTACGGTAAAAACTGGTTTAC 813 2793258 NEK1 CCCTGATATCGAGGTAGTAGAAAAA 8142793258 NEK1 GTAGAAAAAGAAGAGCTCCTGTCAT 815 2793258 NEK1ATATACCAGCTCCAGAAGGTCTTTC 816 2793261 NEK1 ACCTTTCTTATTTATCCCGGTCCCT 8172793261 NEK1 GTTCCTACCTCTTTACACGATTCAC 818 2793261 NEK1TATTTATCCCGGTCCCTTGTTCCTA 819 2793261 NEK1 TACCTCTTTACACGATTCACGACCA 8202793264 NEK1 GTCTCTTCTCTCACTTATGACCTCT 821 2793264 NEK1CTCTTCTCTCACTTATGACCTCTTC 822 2793264 NEK1 TCTCTTCTCTCACTTATGACCTCTT 8232793266 NEK1 ACTAGTACAATGTATGGTACACAAT 824 2793266 NEK1TCGGAATGTCCTCAGTATTTTTCAG 825 2793266 NEK1 CCTTACAGGAGGAAGACACAAAATG 8262793266 NEK1 AAACTCGTTGGATTCGTCTCGGTAA 827 2793267 NEK1CCTTATGGAAATCGTATATTCTTTA 828 2793267 NEK1 CGGACGGCGATTTATACCTTATGGA 8292793267 NEK1 ATACCTTATGGAAATCGTATATTCT 830 2793267 NEK1TTTCGGACGGCGATTTATACCTTAT 831 2793268 NEK1 CGAAGTCCTGTTTTGAGCTAAAGAC 8322793268 NEK1 GAGCTAAAGACAATACGGACGAGTC 833 2793268 NEK1CCTGTTTTGAGCTAAAGACAATACG 834 2793268 NEK1 TGGTCGAAGTCCTGTTTTGAGCTAA 8352793269 NEK1 AAGCTTCAAACCTAGTGTCGGATAT 836 2793269 NEK1AAAAGCTTCAAACCTAGTGTCGGAT 837 2793269 NEK1 TGTAAAAGCTTCAAACCTAGTGTCG 8382793269 NEK1 TTCAAACCTAGTGTCGGATATGGTC 839 2793277 NEK1TTGGACCATGACTTCTATTATAGAC 840 2793277 NEK1 GACACAGAAACGTAATAAGGATACT 8412793277 NEK1 AAGGATACTAGAGGCGTCAAACCAC 842 2793277 NEK1GATCCCTATCTGGTAGTCAGTTGAG 843 2793278 NEK1 ACTCGACACATGTGAATTTGTACGA 8442793278 NEK1 TACTCGACACATGTGAATTTGTACG 845 2793281 NEK1AACCTTAACGATCTCAAGAATTATC 846 2793281 NEK1 CCTCTAAAACCTTAACGATCTCAAG 8472793281 NEK1 GATTTCTACCTTGTCATGTTGAACC 848 2793281 NEK1CTACCTTGTCATGTTGAACCTCTAA 849 2793282 NEK1 CCGGGACTTTGTACATGTACTATCT 8502793282 NEK1 AGAAGTAGCTCTGTAATTTAGAGTC 851 2793282 NEK1AAAACCTGACCAAACATGTCTATAC 852 2793282 NEK1 CTTTTTAAGAAGTAGCTCTGTAATT 8532793284 NEK1 CCTCCCCTAGACAAATTCGCTTATT 854 2793284 NEK1GTATCATTACCTAATGACACTCCCT 855 2793284 NEK1 GTCTTTCCGCAAAACAAAGTTCTCC 8562793284 NEK1 TTTACCGAGAGAGATGTATCATTAC 857 2793287 NEK1CTCTTCAACGTCATAACCGTTTGTA 858 2793287 NEK1 CTCTCTTCAACGTCATAACCGTTTG 8592793287 NEK1 TCTCTTCAACGTCATAACCGTTTGT 860 2793287 NEK1TCTTCAACGTCATAACCGTTTGTAC 861 2793288 NEK1 ACCTCTTCATACAATCTGATGTCTT 8622793288 NEK1 AGATGTCTTCTACCGTCTGTCATAC 863 2793288 NEK1CCGTCTGTCATACAATAGTTCCTTT 864 2793288 NEK1 TTCGGTAAGAACAATTTAGATGTCT 8652793289 NEK1 GTATAGACATTTCTACGGAATCTTT 866 2793289 NEK1GATCGTATAGACATTTCTACGGAAT 867 2793289 NEK1 ATTTACAGATCGTATAGACATTTCT 8682793289 NEK1 ACAGATCGTATAGACATTTCTACGG 869 2793293 NEK1GGATGATTGCAGGACACAGTGACTC 870 2793293 NEK1 CAGTAGTGGCAATAAGGATGATTGC 8712793293 NEK1 CGGTGTGGATCTGACTACGAATAAT 872 2793293 NEK1TTACGCCCTACCATGGAGACGAAAT 873 2793294 NEK1 GACGACGACCAATCTGTCAGAACCA 8742793294 NEK1 CTCTCAGAGTCACGGGGGAAAGTCA 875 2793294 NEK1ACGGGGGAAAGTCAGACCTGACACT 876 2793294 NEK1 ACGACCAATCTGTCAGAACCAAAGA 8772793295 NEK1 AATCAGGCGTAAGCGAGGTCCCAAA 878 2793295 NEK1CGTGCACCGTCAGTTCATCGAAGGG 879 2793295 NEK1 TCACAGCTGGACAGAATGCCCGCAG 8802793295 NEK1 CACCGGTGATCGTTGCTGGAGACAC 881 2806469 IL7RGGATCTAGATTCGAAGAGACAGAAG 882 2806469 IL7R GTAAGTAAAGTATGTGTGACCGAGT 8832806469 IL7R AAGTAAAGTATGTGTGACCGAGTGT 884 2806469 IL7RGGGATCTAGATTCGAAGAGACAGAA 885 2806470 IL7R AATGAAGTTCAGCAAAGACCTCTTT 8862806470 IL7R ATGAAGTTCAGCAAAGACCTCTTTC 887 2806470 IL7RGATCCATGTTGAAAACCGTACCAAA 888 2806470 IL7R TGAAGTTCAGCAAAGACCTCTTTCA 8892806471 IL7R GAGTAAGAGTACGATATCGGTCAAC 890 2806471 IL7RTGAGTAAGAGTACGATATCGGTCAA 891 2806472 IL7R AAAACTCCTGGGTCTACAGTTGTAG 8922806472 IL7R CTGGGTCTACAGTTGTAGTGGTTAG 893 2806472 IL7RCTACAGTTGTAGTGGTTAGACCTTA 894 2806472 IL7R TTGTAGTGGTTAGACCTTAAACTTT 8952806474 IL7R ACCTCTTTTCTCAGATTGGACGTTT 896 2806474 IL7RCGTTATATACACACTTCCAACCTCT 897 2806474 IL7R GACGTTTTTTTATCTGGATTGGTGA 8982806474 IL7R CTCTATATAAAGTAGCTCTGTTTCT 899 2806477 IL7RATTTTCAAAATTACGTGCTACATCG 900 2806477 IL7R AACTGGACTCACAGCAGATAGCCCT 9012806477 IL7R TCACAGCAGATAGCCCTTCCTCGGT 902 2806477 IL7RATCGAATGGCGGTCCTTTTCCTACT 903 2806479 IL7R TTAAATAGGTCGTGTTTCGACTGTG 9042806479 IL7R GTACACTTAAATAGGTCGTGTTTCG 905 2806479 IL7RACACTTAAATAGGTCGTGTTTCGAC 906 2806479 IL7R ACTTAAATAGGTCGTGTTTCGACTG 9072806480 IL7R CATACTCTAATTTCAAGCTAGGTAG 908 2806480 IL7RTCTTTCGAGGTTGGCCGTCGTTACA 909 2806480 IL7R GAGGTTGGCCGTCGTTACATACTCT 9102806480 IL7R GCTAGGTAGGGACTAGTGATAAAAT 911 2806485 IL7RGGGTCAGAGGGGCTAGTATTCTTCT 912 2806485 IL7R ATTCGGATAGCATACCGGGTCAGAG 9132806485 IL7R CAGAGGGGCTAGTATTCTTCTGAGA 914 2806485 IL7RCTAATTCGGATAGCATACCGGGTCA 915 2806486 IL7R AACCCTGATGTTTGTCGTGCGACGG 9162806486 IL7R TTGGGTCAACGAGTCCCAGTCGGGT 917 2806486 IL7RCCTTAGGACTGTAACTTGGGTCAAC 918 2806486 IL7R GGACCTGACGGTCTAAGTATCCCAC 9192806487 IL7R GCAGTGATCATTGTCCCACACGGAT 920 2806487 IL7RGGGACCTGTACCCATGCAAACTGCT 921 2806487 IL7R ATGGCACTCGCTGTTTCTACTAAAT 9222806487 IL7R ATACCCGACAAGTCTCCACGTGTGG 923 2858024 PLK2ACTGGTAAAATTTGGCAACCGTTAT 924 2858024 PLK2 ACAACTGGTAAAATTTGGCAACCGT 9252858025 PLK2 GTACACCACCATGCTTTTGTTAAGG 926 2858025 PLK2TGTCCGATTCCGTATGTCAAGAACT 927 2858025 PLK2 GCATTGACACTTGATACCGGTATAT 9282858025 PLK2 CTGAAAAGCTTACCTGGGATACCCT 929 2858026 PLK2CGGGACTTGTACGAGAATGTTTCTA 930 2858026 PLK2 AGTTACTCCTATCCTATAGATGTTG 9312858026 PLK2 TTTAGCTTACCTTATACGGGACTTG 932 2858026 PLK2ACTTCTTATGGAAGAGTGGATGTAG 933 2858028 PLK2 ACGAGAAATTACTACCGTGGAAAGT 9342858028 PLK2 CGATTTTAGACTATTCCGGGATTAC 935 2858028 PLK2CACCTCTAGACGGATCACAATGACT 936 2858028 PLK2 CACAATGACTATAAGCTTCTGGAGC 9372858029 PLK2 AAACATCCGTGATTGAGTGAGAGGA 938 2858029 PLK2TTGAGTGAGAGGATTAGAGAAGGTC 939 2858029 PLK2 TTATTATTATCTCACGTACGATGTT 9402858030 PLK2 TGTCAAGTGATAATGCGTCTCGAAC 941 2858030 PLK2AGTTCACTGCCACGACTTTATGAAA 942 2858030 PLK2 AATGCGTCTCGAACCGGTTACGAGT 9432858030 PLK2 AGGACTCGTTAAATAATCAGTTCAC 944 2858031 PLK2AAAGTCACCCAGTGGTTTACCCAAC 945 2858031 PLK2 TGGCAGCCACAGGAAAAGTTGTTAC 9462858031 PLK2 AACCCATGGTCGAGAGTCTGGTGTG 947 2858031 PLK2AAGTTGTTACCACGAGTGTACTCGG 948 2858032 PLK2 GTACCCTTCACAACGTCTGTGTCAC 9492858032 PLK2 CTGTGTCACCGTTCCCAAGAAGCCC 950 2858032 PLK2TCATGGTACCCTTCACAACGTCTGT 951 2858032 PLK2 AACTTCTGTCATGGTACCCTTCACA 9522858034 PLK2 GTCTAACCCCTACGATAAGCCTACT 953 2858034 PLK2TCCAGACCTTGTGGGCGTCATCTTT 954 2858034 PLK2 CCTACGATAAGCCTACTATCAGTCT 9552858034 PLK2 CCTTGTGGGCGTCATCTTTTGTTCG 956 2858035 PLK2TGACGCAATAGAAAATAGACCGAAC 957 2858035 PLK2 ACGGAGTGAGAGTAGAATTAGACCT 9582858035 PLK2 CGAAAAACTACTCGAAAGGGTCGTT 959 2858035 PLK2CGTACGTTCACTCAAATGACGCAAT 960 2858036 PLK2 CTTTTTCTGAAGTTATTGAGTCGTT 9612858036 PLK2 CTTCTGTAGATGTTCGAATCCGTAC 962 2858036 PLK2TAGATGTTCGAATCCGTACTAAACT 963 2858036 PLK2 TCTGAAGTTATTGAGTCGTTGGGTC 9642858037 PLK2 GTTTCGTTCTATATAACTGTGTGTA 965 2858037 PLK2TTTCGTTCTATATAACTGTGTGTAT 966 2858038 PLK2 CGACAACAGTATGTCAAGGTCTAAA 9672858038 PLK2 CAAGGTCTAAAGGTGAATAGTTCGG 968 2858038 PLK2GAATAGTTCGGGTCGATTCTTAAAG 969 2858038 PLK2 GAGGCCTGTCTGACAGAAGATCGAC 9702858040 PLK2 TCGTTCCATATGTTACGGCAGGAGT 971 2858040 PLK2GGTCTCCTAGCAGGGTCAAACCTAC 972 2858040 PLK2 CCTACTGTAGTAAGCTGTACTGAAA 9732858040 PLK2 CGAGGACGGTTCGTGAATTAACGAT 974 2858042 PLK2TGCTATACACCATGGGGTTTAATAG 975 2858042 PLK2 ACACTTAGTCTGTAAACCCGGGACC 9762858042 PLK2 AATAGAGAGAGGACTTCAGGAGTTG 977 2858042 PLK2TTCAGGAGTTGTTTGTTCCTGTACC 978 2858044 PLK2 CCGTCGGTCCGATCTTGGGAACCTT 9792858044 PLK2 CTTGAAAAAATAATTACTTCGGTAC 980 2858044 PLK2CCTGAAGCCAGACCGTCGGTCCGAT 981 2858044 PLK2 TCCGATCTTGGGAACCTTGTGTCTT 9822858045 PLK2 TGCGGTTTTCGACTCAAAACACAAT 983 2858045 PLK2CATTCAGTAACTGCGGTTTTCGACT 984 2858046 PLK2 GGTCTTCAAGCTATGATGGAGTCCG 9852858046 PLK2 ATGGAGTCCGTCTAACACAGACCTG 986 2858046 PLK2TTCAAGCTATGATGGAGTCCGTCTA 987 2858046 PLK2 AACACAGACCTGACTTTATGGAAGT 9882858047 PLK2 CATTCACAGTTGAGGATAAACTCTT 989 2858047 PLK2TCTCATAAAATAGACCCTAAAATCG 990 2858047 PLK2 GGGCTTAATTGTACCATAAGTTTCT 9912858047 PLK2 CTCTTGTAAACGAATGGGGCTTAAT 992 2858048 PLK2ACGTCAAAATGGTGATGAAGCTCCT 993 2858048 PLK2 CTTTTGTAAATGTAAGAGAACCTTA 9942858048 PLK2 AAGAAGTAGTATTCGTACATCACGT 995 2858048 PLK2AGAGAACCTTATGACGTCATCTTCC 996 2858049 PLK2 ACTGAGAACTCATTTCATAAAAGAA 9972858049 PLK2 CACGCATACTGAGAACTCATTTCAT 998 2858049 PLK2TTTACAGAAGACGTACACATTAGTG 999 2858049 PLK2 GAAGACGTACACATTAGTGACCGAA1000 2858050 PLK2 CGTCTCATCGATTTGGAGTAGTTTC 1001 2858050 PLK2TGCGGCGTTTTTAATAAGGAGTGTC 1002 2858050 PLK2 TATTGTTTCAGATGCGGCGTTTTTA1003 2858050 PLK2 AACGTTTTACAATGCTCTACTGTCT 1004 2858051 PLK2ATAGACGAGGGTCCCTTAAAAGGAC 1005 2858051 PLK2 AAGTACTCCCTCGAAATTGCTTCAG1006 2858051 PLK2 CGGCAGGTAAAAACACGGTAGGAGT 1007 2858051 PLK2GAGTTAAGGCAGAGCCGAAACAAAG 1008 2858052 PLK2 GGTGCTGACCCTTCGCGATGACGGC1009 2858052 PLK2 TGAGCTTCTTCTTCGCCGGCGGCGT 1010 2858052 PLK2TGGTAAGCGTGAGCCCCGGCCTCTA 1011 2858052 PLK2 CCGGCCTCTAGAGCGCCTAATAGCA1012 2858053 PLK2 AGTGAGCGTGTTCACCTGGCCCCAC 1013 2858053 PLK2TCCGTTCCCACGCTCCTGGTGCCGG 1014 2858053 PLK2 TGGTGCCGGCCGAGCCTGCACACTG1015 2858053 PLK2 GCTCGCGAGAGTGAGCGTGTTCACC 1016 2997377 ANLNTTTAAACTTGCCGACGTCTCCGGCT 1017 2997377 ANLN CTTTAAGTTTAAACTTGCCGACGTC1018 2997377 ANLN ACACCCTCTCAAGGGGGCGGAGTCT 1019 2997377 ANLNGGCTCAGGCAGTGACCTTCGGCTCT 1020 2997378 ANLN TAGCAGAGCATCAGGCTGCGGACCC1021 2997378 ANLN TGTGTGACTCGACTCTGAGTGAAAA 1022 2997378 ANLNCTTGGTGGCAAAGGTAGCAGAGCAT 1023 2997378 ANLN GGACTTAAACTTGGTGGCAAAGGTA1024 2997379 ANLN CCTCCTTCCGAAACTCAGACAGGAT 1025 2997379 ANLNAGGATTTTCCGACAACGCTCTCCAG 1026 2997379 ANLN TCCGACAACGCTCTCCAGAAAGTCG1027 2997379 ANLN ACTCAGACAGGATTTTCCGACAACG 1028 2997380 ANLNAGGACCGCGTCGTTCTCACTCCGCG 1029 2997380 ANLN GCCTTGCCCAGGACGACCTTCGTCG1030 2997380 ANLN CGGGCGTCCCCTCTACGATTACTTT 1031 2997380 ANLNCACTAAACGCCTCAAGTGCGTCGGG 1032 2997381 ANLN GCTTGGGCACGGTCCGCTCTCTTAG1033 2997381 ANLN TTGACGACCTCGCTTGGGCACGGTC 1034 2997381 ANLNGACGACCTCGCTTGGGCACGGTCCG 1035 2997381 ANLN CGGTCCGCTCTCTTAGAAGTCTCTT1036 2997382 ANLN GTCGTCGAGGTTCCAGATACTGAGT 1037 2997382 ANLNCCAGATACTGAGTACGATTCGCTCG 1038 2997382 ANLN GAGTACGATTCGCTCGATCTGTCGG1039 2997382 ANLN GATTCGCTCGATCTGTCGGTGAAAG 1040 2997384 ANLNTCTTTAGAACATGTTTTGGTAGCGG 1041 2997384 ANLN ACCTTTTATTTGTTGGTCAACTCAG1042 2997384 ANLN AACAAGAGGTTCAGGACACAGAGGA 1043 2997384 ANLNAGCGGTAGTTTTTTTGCGACAAGAC 1044 2997385 ANLN TTGAACGTCTCGTTGCCGCGGCAAC1045 2997385 ANLN CGGTGTTCGTCGTCTATGGTAGTCA 1046 2997385 ANLNCACTAAGACAACGACAGGGCCGTAG 1047 2997385 ANLN GCGGCAACCCTATTACTACTATACT1048 2997387 ANLN ACGACGTTGATAAACGAGGACCCTT 1049 2997387 ANLNCGAAAGTTTACGGAGCCGTTGAGGT 1050 2997387 ANLN TTACGGAGCCGTTGAGGTCAACCGT1051 2997387 ANLN GTCTTCCCCGGCAGACCGGTTAGAA 1052 2997388 ANLNCGGGATAGGAGTTCACGACTACTAC 1053 2997388 ANLN CTACCGCTACGGAGAAACTTATTTC1054 2997388 ANLN CGGACCATGGCGAACAAATAGGTTT 1055 2997388 ANLNCACAATTCGTCCTTCGATGTAAGAC 1056 2997389 ANLN AATAGGGTCTGTCAAGGTAGGTTCC1057 2997389 ANLN CCATAGCTTTGGTTAACACTTCAGT 1058 2997389 ANLNTCAACACTCCCTGTTTTAGGACTCG 1059 2997389 ANLN AGGTCACTTTAGATGATGTAGATAG1060 2997391 ANLN CGAAACCTCTCGCAACAGTTCTTGT 1061 2997391 ANLNTCGGAAAGGACCTTGCGAAACCTCT 1062 2997391 ANLN GTTTCTTTCAGGTCGAGCATCGTGT1063 2997391 ANLN GAGGTTTATGTTTCCGGTAGGTTCT 1064 2997393 ANLNCCCGTTATATACCTCACGTCTTTTT 1065 2997393 ANLN CGGCTAAACTGTTCCCGTTATATAC1066 2997393 ANLN TCTTGATCGTACAGAAGCACCGGCT 1067 2997393 ANLNCACGTCTTTTTCCGCCTTTGAGTTT 1068 2997394 ANLN TCCACTGGCTTTTGGTCTATGGTCG1069 2997394 ANLN AAAGTTTTTGAGTCAGTGAAGGTCA 1070 2997394 ANLNTATGGTCGGTTTTTAAGATCATGTC 1071 2997394 ANLN CAAAGTTTTTGAGTCAGTGAAGGTC1072 2997395 ANLN GTAGTCTGGGTTTCCAACTCGTCTT 1073 2997396 ANLNAGAAGTCACTACAGGATCTCCTTCC 1074 2997396 ANLN CGTGACTTATAGAGGAGTTACAGAA1075 2997396 ANLN CCTAGTTCGTAATCGTCTTTCGTCG 1076 2997396 ANLNAACGTGGTAACCGTGTTTGTCAACC 1077 2997397 ANLN GTGGATCTGACCTTAACTTTCTGTG1078 2997397 ANLN CTGACCTTAACTTTCTGTGGTCGTC 1079 2997397 ANLNTCAAATCACAGGTGTGGATCTGACC 1080 2997397 ANLN AGGTGTGGATCTGACCTTAACTTTC1081 2997399 ANLN CTTTGTCTTGCAGGTAGTTATTTCG 1082 2997399 ANLNTTGCAGGTAGTTATTTCGTCCACTA 1083 2997399 ANLN ACTAACAAGCCTTCCTTCTACAATG1084 2997399 ANLN AAGTTTCTTTGTCTTGCAGGTAGTT 1085 2997400 ANLNTCGTCTTTCTGAAGAAGATTAACGT 1086 2997400 ANLN TGTCTGTCACTAGATAGTTCGATCG1087 2997400 ANLN CTTGAGTTATTGCTTTATTTATACG 1088 2997400 ANLNTCGATCGGTCCGAGAATTGACGACA 1089 2997402 ANLN ACGGTAGGTTTCCTAGTCAATGAAA1090 2997402 ANLN AGGCGAACGGAGATTTTCGTCTAAA 1091 2997402 ANLNAATGAAACAGTCTTTAGGCGAACGG 1092 2997402 ANLN GTCTAAAACAGACGTCATGCCAAGT1093 2997403 ANLN GAGAATTGCCACTACGAGACTGTAA 1094 2997403 ANLNTACCATCGGTGTGGTAATCGTTCAT 1095 2997403 ANLN GACTGTAAGTGATGATGTAAATGAG1096 2997403 ANLN AGTTTGAGAGAATTGCCACTACGAG 1097 2997406 ANLNTTTCTAGGGAGTCCGGAACTATTCT 1098 2997406 ANLN TTCTTTCTAGGGAGTCCGGAACTAT1099 2997406 ANLN TCTAGGGAGTCCGGAACTATTCTTC 1100 2997406 ANLNCTTTCTAGGGAGTCCGGAACTATTC 1101 2997408 ANLN CACGACACGCTTGGTCGTTGAAGCG1102 2997408 ANLN CCGGTCAGGTCCTCCAGAATCACGA 1103 2997408 ANLNAACCTAGAATGTGTAATAGTAACAG 1104 2997408 ANLN CGTTGAAGCGGGAACAACCTAGAAT1105 2997409 ANLN CGCTCTCGATGACCCGATAAACAAG 1106 2997409 ANLNATTCTCTCGCTCTCGATGACCCGAT 1107 2997409 ANLN TCGATGACCCGATAAACAAGGTCCT1108 2997409 ANLN ATGACCCGATAAACAAGGTCCTTTT 1109 2997414 ANLNAGAATAACCTGAATAGGTCTACTAC 1110 2997414 ANLN CAAAACCACGGACCGTAGCTTCTAC1111 2997414 ANLN GACCTTTGACATATAGAATAACCTG 1112 2997414 ANLNCCGTAGCTTCTACCACACAAGAAAG 1113 2997417 ANLN GACCCCGAGTAATATGACAACAAAC1114 2997417 ANLN AACCGACAACCGAGTACACACGGAT 1115 2997417 ANLNACCGTTCTCGATGGTCAACTATAAA 1116 2997417 ANLN GCATAGTATCCTTAAGTACCGACGG1117 2997418 ANLN GTATCCTTCCTATTTAGACCGATTA 1118 2997418 ANLNCCTTCCTATTTAGACCGATTAACAT 1119 2997418 ANLN ATCCTTCCTATTTAGACCGATTAAC1120 2997418 ANLN CCTATTTAGACCGATTAACATGGTC 1121 2997419 ANLNCACGTTCTGCGTTGTGAAAACTTAA 1122 2997419 ANLN AGGCTGGTGTTTCTCTTCTACTGGC1123 2997419 ANLN TGGCTCTCTGAGAACAGTCGGTTAC 1124 2997419 ANLNTCGGTTACGTCCCTGTGTGAGACAC 1125 2997422 ANLN TTCTCGCCCTAGAGACCTACGTTTT1126 2997422 ANLN ACCTACGTTTTTGAGTTAGTTCAAG 1127 2997422 ANLNTCAAGAACAACTATAAGCGGAGACC 1128 2997422 ANLN ACCGACAGACGTCTATGATTTCTTC1129 2997423 ANLN ACGATGTTTGGATAACCTTTCGGAA 1130 2997423 ANLNCGATGTTTGGATAACCTTTCGGAAT 1131 2997423 ANLN AACGATGTTTGGATAACCTTTCGGA1132 2997424 ANLN GACGCATCGAATGTCTGAATCGTAT 1133 2997424 ANLNATGCTTTCCCAAACACGGTTATAAG 1134 2997424 ANLN AGAGTCATCAAAAAAGCTTTCCGAC1135 2997424 ANLN CAGAAGAACCTCGACATCCAGAACT 1136 3012979 GNG11CGACGTCAGTGTAGGACGCGCCCAC 1137 3012979 GNG11 GAGTCCAGGATCCTTCGACCCCGTG1138 3012979 GNG11 GCACTGTTCGCAGGGCCTCTTTCGG 1139 3012979 GNG11GGTCCGGAAGTCAACAAAGCCCTGC 1140 3012980 GNG11 ACTTTTACCTTCAACTCGTCGAAGC1141 3012980 GNG11 TCAACTCGTCGAAGCGTTTCTTCAC 1142 3012980 GNG11ACCTTCAACTCGTCGAAGCGTTTCT 1143 3012980 GNG11 TCGTCGAAGCGTTTCTTCACTTCAA1144 3012981 GNG11 TCTCCTAGGAGATCATTTCCCTTAA 1145 3012981 GNG11ACCTCTCCTAGGAGATCATTTCCCT 1146 3012981 GNG11 CTCCTAGGAGATCATTTCCCTTAAG1147 3012981 GNG11 CCTCTCCTAGGAGATCATTTCCCTT 1148 3012982 GNG11CTGTGAAGAAAGTCATATAACGAAC 1149 3012982 GNG11 CACGATGAGTAGAAACGAGTGATAC1150 3012982 GNG11 CTTGTAATGAACTCGTACTGTGAAG 1151 3012982 GNG11ACCCTCTTTGACGTAGGATTCACCT 1152 3012983 GNG11 GAACCCGTACCGTGATGAGGTCAAG1153 3012983 GNG11 GAACCTGGAGACGTGAGTACGAACG 1154 3012983 GNG11CGAAACTCTCGGTCATGAATAAGGA 1155 3012983 GNG11 GGAGACCTTGCACAAACTAGATTGG1156 3012985 GNG11 GTAAATAAGGCCAATGACCGTTCCG 1157 3012985 GNG11CATGTGAGGGTTCAGGATCGAAAAC 1158 3012985 GNG11 GGGATTGAACAACCCTCAACGCTAA1159 3012985 GNG11 GGTCGGTTGTACATCTTCACGTTAT 1160 3428784 DRAM1GAGGCATCAGCGCAGGCGAACCTCG 1161 3428784 DRAM1 TGGCAGGCACTCACATGCGCGGGCC1162 3428784 DRAM1 GCCCGGCGAAACACTGAAGTGAGCA 1163 3428784 DRAM1TGAGCAAAGCGTTGTTCGGGCCCGT 1164 3428785 DRAM1 CGACCCGCGTCGTGAGGCAGCCGCC1165 3428785 DRAM1 ACCCGCGTCGTGAGGCAGCCGCCGC 1166 3428785 DRAM1GGCGACCCGCGTCGTGAGGCAGCCG 1167 3428785 DRAM1 CCCGCGTCGTGAGGCAGCCGCCGCC1168 3428786 DRAM1 GGAAGTAATAGAGGATGCACCAGCG 1169 3428786 DRAM1TGGACCAGCAGTCGGCGGAAGTAAT 1170 3428786 DRAM1 GACACGAAGGACTCCCCTTACCGAA1171 3428786 DRAM1 TAGAGGATGCACCAGCGGCACGAGA 1172 3428798 DRAM1AAACCTAAATACTATTTGAAGAGAC 1173 3428798 DRAM1 AACCTAAATACTATTTGAAGAGACG1174 3428798 DRAM1 AAAACCTAAATACTATTTGAAGAGA 1175 3428798 DRAM1ACCTAAATACTATTTGAAGAGACGT 1176 3428799 DRAM1 AATTGAACCACAGAAATCACGAACC1177 3428799 DRAM1 GGACGATAAAGTCGTGAGGACAAAA 1178 3428799 DRAM1ATCATGTCTTCGTTTTAGTTTGGAC 1179 3428799 DRAM1 CGTCGGTGCTACATATGTTCTATGT1180 3428800 DRAM1 ACCTCACATACACAGACTTCTCTCG 1181 3428800 DRAM1CGTGTGAATACGGTAATATCGGTAA 1182 3428800 DRAM1 GTCAATACTCCTCACCACCTCACAT1183 3428800 DRAM1 CTCCGTGTGAATACGGTAATATCGG 1184 3428802 DRAM1GGGTCACCTTGTCAGAGAGCTGTAC 1185 3428802 DRAM1 AGACGGCAAAGAACGCGTCGACAGT1186 3428802 DRAM1 CACATGTGCGAGGATGTCAGGTAGT 1187 3428802 DRAM1AGAGCTGTACGGTGTATGCCTACCA 1188 3428806 DRAM1 GTGATTAAAGGTATTGGTTCGACCT1189 3428806 DRAM1 TGATTAAAGGTATTGGTTCGACCTC 1190 3428806 DRAM1GATTAAAGGTATTGGTTCGACCTCA 1191 3428809 DRAM1 ACTCAGAAAAAGCCGATTTAAGACA1192 3428809 DRAM1 TCATACATGTAATTTCACTCAGAAA 1193 3428809 DRAM1GTAATTTCACTCAGAAAAAGCCGAT 1194 3428809 DRAM1 TCACTCAGAAAAAGCCGATTTAAGA1195 3428812 DRAM1 GTGGGATTCCTATAGGTGTCTTTAG 1196 3428812 DRAM1CAGTGGGATTCCTATAGGTGTCTTT 1197 3428812 DRAM1 TCACAGTGGGATTCCTATAGGTGTC1198 3428812 DRAM1 CACAGTGGGATTCCTATAGGTGTCT 1199 3428813 DRAM1GAGTGAGTCACTTACAGCGTCCGGT 1200 3428813 DRAM1 TGGGACTAATAACCCTACGTAGACG1201 3428813 DRAM1 CGAGAACGACGATTAACGGGTAAGC 1202 3428813 DRAM1GGACGAGTACTCCAGCGTGGAAAAC 1203 3428814 DRAM1 GTCGGTTCTTCTTGAAGACCCAAGT1204 3428814 DRAM1 TCGGTTCTTCTTGAAGACCCAAGTC 1205 3428815 DRAM1CCGACCTACAGGGTGTTGTGATATT 1206 3428815 DRAM1 CAGTTCGGGAAACACAATTCGTTCT1207 3428815 DRAM1 TGAGGTAGAAAAGTGGGTTTAGTAC 1208 3428815 DRAM1ACGAGGAAGAGAAGTACGGACACCG 1209 3428816 DRAM1 ACACCGGTTCACTCTAGTCGGGAGT1210 3428816 DRAM1 TCGTCGGGTACATCTGTCGAAGCCT 1211 3428816 DRAM1CAAGCCCCATCGAGGAGTAATTGAT 1212 3428816 DRAM1 GATCTCGTATTTGGGTACACACCGG1213 3428817 DRAM1 AAGAAATTCTGCGTAGTATTTACCA 1214 3428817 DRAM1ACGAAAGAAATTCTGCGTAGTATTT 1215 3428817 DRAM1 GAAAGAAATTCTGCGTAGTATTTAC1216 3428817 DRAM1 GAAATTCTGCGTAGTATTTACCAAA 1217 3428818 DRAM1TCTGAAAACAAGAGCCGCGAGGAGT 1218 3428818 DRAM1 AGGAGTGCTACCTCAAAGTACGAAG1219 3428818 DRAM1 GTGTTAATCTAACCCTCGAGGAACT 1220 3428818 DRAM1ACGGAGTGAAGCTCGTCTGAAAACA 1221 3428832 DRAM1 TATTTTGGTATAAACTGACGTGGAA1222 3428832 DRAM1 ATACTTGGTGTGACTTTGCTGGAAG 1223 3428832 DRAM1ATCAGTTCACGACGTATTACAAAAC 1224 3428832 DRAM1 TCAACTACCGTTGCTACCAATGAGT1225 3454842 BIN2 GGGACCCAAGAGTCATCCTTACGAC 1226 3454842 BIN2CTCTTTGATGGTTCTGAGGAGGACG 1227 3454842 BIN2 AGTCTCCCTATATTCTCGGTCGTAG1228 3454842 BIN2 ACGACCACGACAGATTTCTGGACCG 1229 3454844 BIN2CTGGTCGAAGTTCAGAGGTACCATG 1230 3454844 BIN2 TCTGGTCGAAGTTCAGAGGTACCAT1231 3454844 BIN2 TGGTCGAAGTTCAGAGGTACCATGG 1232 3454844 BIN2GGTCGAAGTTCAGAGGTACCATGGT 1233 3454845 BIN2 ATTCGAATAGAGTCGATTGAGGAGC1234 3454845 BIN2 CCTATTATTCGAATAGAGTCGATTG 1235 3454845 BIN2ATTATTCGAATAGAGTCGATTGAGG 1236 3454845 BIN2 TTCCTATTATTCGAATAGAGTCGAT1237 3454846 BIN2 TTGGTGGTCTCTTCGGTCATTCTTG 1238 3454846 BIN2AACATGAAGGGGGTGGAATTACTGT 1239 3454846 BIN2 TCGGTCATTCTTGAGGACTCCGGTT1240 3454846 BIN2 CTTTTGTAGGTGTTAGTCTTGGGAC 1241 3454847 BIN2ATGGAAGGTCGGGATGTCGGAGACC 1242 3454847 BIN2 GTCGGGATCCCGGAGGAACCCCTGA1243 3454847 BIN2 CCTGGAGGGATCTCCAGAGAGGATT 1244 3454847 BIN2ACCCTGACGTTCAGGATCCTGGAGG 1245 3454848 BIN2 TCTCTCGGAGATAGGTCTCCTGGAG1246 3454848 BIN2 CTTCTCTCGGAGATAGGTCTCCTGG 1247 3454848 BIN2TTCTCTCGGAGATAGGTCTCCTGGA 1248 3454849 BIN2 TGAGGTAGTGGTCCGCCTCGGGACT1249 3454849 BIN2 AGAGGATGGTGACTTTCCCGGTTCA 1250 3454849 BIN2GGTCGAGGTGTTGAGGTAGTGGTCC 1251 3454849 BIN2 GATGGTGACTTTCCCGGTTCAGGGT1252 3454850 BIN2 CAGAGGTCAGGAGAATGGAGTGGAT 1253 3454850 BIN2TGTCGATGTCAGAGGTCAGGAGAAT 1254 3454850 BIN2 CTTGTCGATGTCAGAGGTCAGGAGA1255 3454850 BIN2 AAGCTTGTCGATGTCAGAGGTCAGG 1256 3454851 BIN2GTCGTCCGCGAGAAATCAGTAAAGA 1257 3454851 BIN2 TCCGCGAGAAATCAGTAAAGAGGGG1258 3454851 BIN2 CGTCCGCGAGAAATCAGTAAAGAGG 1259 3454851 BIN2CGCGAGAAATCAGTAAAGAGGGGGT 1260 3454853 BIN2 GTAAAGGTTGAACTCCCTACAGAAG1261 3454853 BIN2 TAACCGACGATACACTGGTAGAAGG 1262 3454853 BIN2TGAACTCCCTACAGAAGATGTCCCT 1263 3454853 BIN2 AGCATAACCGACGATACACTGGTAG1264 3454854 BIN2 TAAATCCTCGGAACCACCGACCAAA 1265 3454854 BIN2ACGGAATGAGCATACACAAACACCA 1266 3454854 BIN2 TACCGAAAGTAAATCCTCGGAACCA1267 3454854 BIN2 GAAAGGGTACGGAATGAGCATACAC 1268 3454855 BIN2CTTCTCAAGTTGTTTCGGGTCTGAC 1269 3454855 BIN2 TCTTGATGATCTCCTCGACGGATAA1270 3454855 BIN2 CTTCTAGACTTGGTTCTTGATGATC 1271 3454855 BIN2TCCTCGACGGATAAGAAATATTATC 1272 3454856 BIN2 AGCCTTTGAGCACCTGATACTGTCA1273 3454856 BIN2 CCAGCCTTTGAGCACCTGATACTGT 1274 3454856 BIN2CCCAGCCTTTGAGCACCTGATACTG 1275 3454856 BIN2 GCCCCAGCCTTTGAGCACCTGATAC1276 3454857 BIN2 TACAACGGGTCAAGTCACTTTAATT 1277 3454857 BIN2ATACAACGGGTCAAGTCACTTTAAT 1278 3454857 BIN2 ACAACGGGTCAAGTCACTTTAATTC1279 3454858 BIN2 TTCACCTCGGAAGTGGTCGGAGACT 1280 3454858 BIN2GTGTGACACGTAAACACATCGGAGT 1281 3454858 BIN2 CACCTAGGGAGATTAAAACTGGGAG1282 3454858 BIN2 CTGGAACACGGGACAAGAATTAGAG 1283 3454859 BIN2GTCGCTCACCCTGCCAGTACTCCTC 1284 3454859 BIN2 TGTCGTCGCTCACCCTGCCAGTACT1285 3454859 BIN2 ACGTACTTTCAAGTTTTTCTCACAG 1286 3454859 BIN2TAGATGTCGTCGCTCACCCTGCCAG 1287 3454860 BIN2 ACTTCTTGAAGGAATCACGTCAGTT1288 3454860 BIN2 TTCTTGAAGGAATCACGTCAGTTTC 1289 3454860 BIN2CTTCCGGTGTTCGACATGTTCCTGG 1290 3454860 BIN2 GGTGTTCGACATGTTCCTGGACTTC1291 3454862 BIN2 CTTGCTAAACTTGTTTCGCGATCGT 1292 3454862 BIN2CTAAACTTGTTTCGCGATCGTTGAA 1293 3454862 BIN2 TGCTAAACTTGTTTCGCGATCGTTG1294 3454862 BIN2 ACTTGCTAAACTTGTTTCGCGATCG 1295 3454863 BIN2GGATACCCTTCCAGATCGAGCTTTG 1296 3454863 BIN2 GCACATCGGTCTGAAGCAATGAAGT1297 3454863 BIN2 CTCGTGACGAAACTCGGGACCCTTC 1298 3454863 BIN2GGTCGAGAGGGCTCAACTAAATAGT 1299 3454864 BIN2 ACGTCTTCTTCAAATCGTCCCGGGT1300 3454864 BIN2 GCCGCGCCGGCCGGAGAAGCGGTTC 1301 3454864 BIN2TCTTCTTCAAATCGTCCCGGGTCCT 1302 3454864 BIN2 CACGTCTTCTTCAAATCGTCCCGGG1303 3454865 BIN2 CGGCCCTCGGGCGTGAAGGAGGAGC 1304 3454865 BIN2TCTTTTGGTGTCCCGCGCCCCGGTC 1305 3454865 BIN2 AGTCTTTTGGTGTCCCGCGCCCCGG1306 3454865 BIN2 GCCCTCGGGCGTGAAGGAGGAGCCC 1307 3454866 BIN2CCGAATCTCGGATGGACCTCGTTCT 1308 3454866 BIN2 AGGGATGGTCAAGGTCCGAATCTCG1309 3454866 BIN2 GAGTCTCTTGGATTTGCACAAAAGC 1310 3454866 BIN2TGCGTCACATGTACCGCCGAAGCGT 1311 3536337 CDKN3 ATCTCCGGCTCAGAAGCCGGTGGGT1312 3536337 CDKN3 GCCTCATTCTTTGGTCTTCGCCTAG 1313 3536337 CDKN3GTGGAGTGTCTTCCTGCTTGGTCAC 1314 3536337 CDKN3 AGCCGGTGGGTTTCCGCCTCATTCT1315 3536338 CDKN3 ACCAGAGCTGCACCCCGCCGGTCGC 1316 3536338 CDKN3CGCCGTGACCAGAGCTGCACCCCGC 1317 3536338 CDKN3 GTGACCAGAGCTGCACCCCGCCGGT1318 3536338 CDKN3 CCTCCGCCGTGACCAGAGCTGCACC 1319 3536343 CDKN3AACATTTAAATTTCTACAATCTTCT 1320 3536343 CDKN3 ACATTTAAATTTCTACAATCTTCTT1321 3536344 CDKN3 TGTTCTGTATAAACAAAAGACGTGG 1322 3536344 CDKN3ACACCATATGTTCTGTATAAACAAA 1323 3536344 CDKN3 TTCTGTATAAACAAAAGACGTGGTC1324 3536344 CDKN3 ACCATATGTTCTGTATAAACAAAAG 1325 3536345 CDKN3AGGGTTTGGAAGACCTAGAGATGGT 1326 3536345 CDKN3 GGGTTTGGAAGACCTAGAGATGGTC1327 3536346 CDKN3 TGGGTAGTAGTAGGTTAGCGTCTAC 1328 3536346 CDKN3AGTAGTAGGTTAGCGTCTACCTCCC 1329 3536346 CDKN3 GTTACACCTTAATAGTGGGTAGTAG1330 3536346 CDKN3 TAATAGTGGGTAGTAGTAGGTTAGC 1331 3536347 CDKN3CTTTATTACCTTCTCGAATGTTGGA 1332 3536357 CDKN3 AGTGGTCTCGTTCGGTATCTGTCGG1333 3536357 CDKN3 CCTAGGCCCCGTTATGTCTGGTAGT 1334 3536357 CDKN3GTCGGACGCTCTGGATTCTCCTAGG 1335 3536357 CDKN3 GACAGACTGTGTTATAGTGGTCTCG1336 3536358 CDKN3 GGTCAGGCAAAACCCTTACCTAGGA 1337 3536358 CDKN3TGAAGAGTCAAAAACGGGGTCAGGC 1338 3536358 CDKN3 CAGGCAAAACCCTTACCTAGGAGAG1339 3536358 CDKN3 GCAAAACCCTTACCTAGGAGAGTGG 1340 3536359 CDKN3TTACTCTACCAATAACAATTATGTT 1341 3536359 CDKN3 GTTACTCTACCAATAACAATTATGT1342 3536359 CDKN3 CTGTTACTCTACCAATAACAATTAT 1343 3536359 CDKN3TGTTACTCTACCAATAACAATTATG 1344 3536360 CDKN3 TATGTTAATAGAAGTACTCAAAGCC1345 3536360 CDKN3 TGTTAATAGAAGTACTCAAAGCCCT 1346 3536360 CDKN3GTTATGTTAATAGAAGTACTCAAAG 1347 3536360 CDKN3 GTTAATAGAAGTACTCAAAGCCCTG1348 3536361 CDKN3 AAGTGTTAGTTCTAGACATAGTTCT 1349 3536361 CDKN3TGTTAGTTCTAGACATAGTTCTATT 1350 3536361 CDKN3 GTGTTAGTTCTAGACATAGTTCTAT1351 3536361 CDKN3 TAAGTGTTAGTTCTAGACATAGTTC 1352 3536362 CDKN3ACGTCTATAAGGATTTCAAAATAAC 1353 3536362 CDKN3 TTACTTTGGTGGTCACAATAGTTGA1354 3536362 CDKN3 TTACATGTACACGTCTATAAGGATT 1355 3536362 CDKN3CTTTACAGTCAAGAGATCGTATTAA 1356 3599812 KIF23 GGCGCGGAATCGGCGCTTCAAGATC1357 3599812 KIF23 ACCGGGCAAACTTTACGCGGTCCGC 1358 3599812 KIF23CCGAAGCGTCTCGTGGCGCGGAATC 1359 3599812 KIF23 CCCGAGAATCGCAGCGGCGGCCGAA1360 3599813 KIF23 AGGGCGTACGCGCAAACCCGCCGCA 1361 3599813 KIF23GTCGGCAGGGCGTACGCGCAAACCC 1362 3599813 KIF23 GCGTCAGAAGCGGTCGGTCGGCAGG1363 3599813 KIF23 AAGAACGACGGCCAGGATTGCAGGG 1364 3599815 KIF23CCCGATGTCTGAGTTGGCTTTACCT 1365 3599815 KIF23 CCCGAAAGGACTAGTTCTCACAACG1366 3599815 KIF23 GTCGAAGTATGAGGACTCCCGATGT 1367 3599815 KIF23ATCCCACGCGGGTGACCCGAAAGGA 1368 3599816 KIF23 TGGTGGGTCTTCCTTGAGAAACTAC1369 3599816 KIF23 TTCATAAACCGTGAGTGTGGTGGGT 1370 3599816 KIF23TTACTGGAGTAAGTACCGTTTTTAC 1371 3599816 KIF23 CTACAACACCGATTAGGGAACCAGT1372 3599817 KIF23 GAGTGTGTTACTGACCAAGAGGTCC 1373 3599817 KIF23GGAGCAACAAACCTGTACTAGAAAT 1374 3599817 KIF23 GTATACCACACTGCCCTTCACCTTT1375 3599817 KIF23 ATCCCAGTAAAGTTCGATTTGCTAT 1376 3599818 KIF23TTTCTCTTCGATACGGGTTAGGTTT 1377 3599818 KIF23 TATATGTCACACTCCAACTACGGAA1378 3599818 KIF23 CTACGGAATAATCTTGCAGTCTTTT 1379 3599818 KIF23CAAAAGTTTAGATTACTATCCTTAT 1380 3599819 KIF23 TTTTACCTGAATATTGCATATGTTA1381 3599819 KIF23 AATTTTACCTGAATATTGCATATGT 1382 3599819 KIF23CTGAATATTGCATATGTTAACTTGA 1383 3599819 KIF23 ACCTGAATATTGCATATGTTAACTT1384 3599820 KIF23 ATACTATTGACATGTTCTTAAGACG 1385 3599820 KIF23CTTCTCCACGGCAAACTAGGGTATT 1386 3599820 KIF23 TCTATCACAGATACCACATAAACAG1387 3599820 KIF23 TGCTGTTCATCTAGGTCTCAAACGT 1388 3599822 KIF23CAGTGAACCGCAAAATCAGGATCAG 1389 3599822 KIF23 ATAAAGAGACCTCATAATATGCAAT1390 3599822 KIF23 CTATGGTCGTAGAGTATTAAATCCT 1391 3599822 KIF23TCAGGATCAGAATTTACTTCTATGG 1392 3599823 KIF23 TACAACGTCCTACATGTCTTCAACT1393 3599823 KIF23 GGAGGTGTTAGATTTAACGAAGCAC 1394 3599823 KIF23AACGAAGCACTTCTATTCTTGGTAT 1395 3599823 KIF23 AACTTCACTTTAGATGACTCCTCCG1396 3599824 KIF23 AAACTGAATAATCTTTCGTACATAT 1397 3599824 KIF23AGTGGATCTCAACGATGATTCAAAC 1398 3599824 KIF23 CGATGATTCAAACTACCGTTAAAAA1399 3599824 KIF23 ACTACTTATAGTGGATCTCAACGAT 1400 3599825 KIF23TAATTTAATCAAGTCCGAGGGAACC 1401 3599825 KIF23 TGGGTAAACTTAGCACTCAGGTCGG1402 3599825 KIF23 CTCTGCATAACGATTATGGGTAAAC 1403 3599825 KIF23GCAAGGGTATCGCACAAGTTGTAAT 1404 3599826 KIF23 GTCTTCCCTTGTCTAATGCACTTCG1405 3599826 KIF23 CACTTTCTTGATTGGCCTGGTCTCG 1406 3599826 KIF23GAACCATCTAGAACGACCTTCACTT 1407 3599826 KIF23 TCTTGTTTAGTGATATTCAGTCAAC1408 3599828 KIF23 GTTTCAATTGGGTAGACAAGTTCTT 1409 3599828 KIF23ACGCCTACTAGCACACACACTTGGG 1410 3599828 KIF23 CCAAGGTATAGCTCTAAGTTTCAAT1411 3599828 KIF23 AGTTCTTGATGAAACTACCCCTTCC 1412 3599830 KIF23TGGTAACCAATGACTGCACCAAAAC 1413 3599830 KIF23 GTAACCAATGACTGCACCAAAACGT1414 3599830 KIF23 GGTAACCAATGACTGCACCAAAACG 1415 3599830 KIF23TAACCAATGACTGCACCAAAACGTC 1416 3599831 KIF23 CTATAGTTGCTACTCGTCTGTGAAG1417 3599831 KIF23 TCTGTGAAGGTTCCGACTAACTTCG 1418 3599831 KIF23TAACTTCGGAATCTCTTTGCTGTAT 1419 3599831 KIF23 GGAAACGGTAGTACGCTTTAAAACC1420 3599832 KIF23 TTACGAAAATTTCGAAACAATGTTC 1421 3599832 KIF23GATTACGAAAATTTCGAAACAATGT 1422 3599832 KIF23 ATTACGAAAATTTCGAAACAATGTT1423 3599833 KIF23 TTCTTTTGGTGTACGTTCCCTTTGA 1424 3599836 KIF23TCTATTTGCGTTAAACGTTGTCCTT 1425 3599836 KIF23 TGTTGATGATAGATACTCCTTCTAT1426 3599836 KIF23 ACCACTGTCTTTGCTGTTACTTCAC 1427 3599836 KIF23ACTGTTTGCGTCTAATCTTCGGTCC 1428 3599837 KIF23 CATCTCACCGTCGGTTTGTCGACCT1429 3599837 KIF23 TCGCATCTCACCGTCGGTTTGTCGA 1430 3599837 KIF23CGACCTCTACGTCTTATTTGAGACC 1431 3599837 KIF23 CTCACCGTCGGTTTGTCGACCTCTA1432 3599838 KIF23 GTCTCTCTGGGAGAGCCCTCGCTCT 1433 3599838 KIF23CTCGCTCTAGCTCTTTTTCAATGAG 1434 3599838 KIF23 TTCGACTTTGTTGACTTCCGATAAC1435 3599838 KIF23 GACTTCCGATAACAATGGCTTGGAT 1436 3599839 KIF23CCCTCCACCAAGGATGTAAGTCTTT 1437 3599839 KIF23 GTAGATAACGTTCCGCATCCGTCGT1438 3599839 KIF23 GTCGGTGTCGATGTATCCGCGAGAT 1439 3599839 KIF23TCCGCGAGATTGAGAACGTCGTCGT 1440 3599841 KIF23 AGACAAAACAAATCTTCGGATCTTT1441 3599841 KIF23 GGAGAGTTATCGTCCCTATTTATAA 1442 3599841 KIF23AACACCTGTATTATCTAATGGAGAG 1443 3599841 KIF23 TCCTTTCTGAACGTCGTAATGGTCT1444 3599842 KIF23 ATTTAATTAAGACCCAATACGAACA 1445 3599842 KIF23TTAATTAAGACCCAATACGAACAAA 1446 3599842 KIF23 AATTAAGACCCAATACGAACAAAGA1447 3599842 KIF23 TAATTAAGACCCAATACGAACAAAG 1448 3599843 KIF23CGGAGGCTACCCCTCTAACTTTGAT 1449 3599843 KIF23 TCTGCTAGTGCGAGACGTCCTCTGT1450 3599843 KIF23 ACCCATCTAGTATTCGGGCGGAGAT 1451 3599843 KIF23GGAGTACGGTAGTGTCATAGACAAC 1452 3599845 KIF23 GTTCCCCACCACCTGTTAGACAAGT1453 3599845 KIF23 TTTTGTTCCCCACCACCTGTTAGAC 1454 3599845 KIF23CAAATGACTATAACTCTGAAATTTC 1455 3599845 KIF23 CCCACCACCTGTTAGACAAGTCAAA1456 3599849 KIF23 CTTTTTAATTTATAAACAGACGGAT 1457 3599850 KIF23ATGGACCTACTGGATTTCTGGAAAG 1458 3599850 KIF23 CTGGAAAGACCGAGTGTTGTAAACA1459 3599850 KIF23 GATAACTCTCCTCGACTAGAAAAAG 1460 3599850 KIF23TGGATCCACACCTCGGACGATTTAT 1461 3599851 KIF23 ACCTATAGTCGTAGTGCGTGTTGGG1462 3599851 KIF23 CTATAGTCGTAGTGCGTGTTGGGTT 1463 3599851 KIF23CCTATAGTCGTAGTGCGTGTTGGGT 1464 3599852 KIF23 AACTTTTAGTGCCTGGAGTCGATGT1465 3599852 KIF23 TACCAAGGTTTCTGTTGATCATAAG 1466 3599852 KIF23GAGCTTTCGGTACGGTCTTCGTCAG 1467 3599852 KIF23 TCTCGTTTCGAAAGGGATACCAAGG1468 3599853 KIF23 TGTAAATCTATACGGTTTTCTTAAT 1469 3599853 KIF23AAATCTATACGGTTTTCTTAATTTT 1470 3599853 KIF23 ACTGTAAATCTATACGGTTTTCTTA1471 3599853 KIF23 AGACTGTAAATCTATACGGTTTTCT 1472 3726377 EME1CTCCTCAACGGTTGTAAACGGAAAG 1473 3726377 EME1 CATCACCAACTGTAGAGTCTAACAC1474 3726377 EME1 TCAATAAAAGTGGTGGACAGGGTCT 1475 3726377 EME1GTCGGTCAGTCCAACGATTCGTCAC 1476 3726378 EME1 AGGTACTATGGGGTCTCTCCTCACG1477 3726378 EME1 ACGTCGTCTATTGTTCCTGGACTAG 1478 3726378 EME1GACTAGAATCTAGGTACGACAGTCG 1479 3726378 EME1 TCGGGAAAGGTTTCTAGGGACTTCA1480 3726379 EME1 TACGTCGTGACCAATGGTCCTACTT 1481 3726379 EME1TGTTCGTTCCGTCTTCCTTTCGTGG 1482 3726379 EME1 TGTGTAGTAACATCACGACCTAGGT1483 3726379 EME1 TCTTTTGGTTCGGCTCAGTCTTCCA 1484 3726381 EME1CGTGACGTCTGGTACCTCACGGCGA 1485 3726381 EME1 GGATCCTCGTGACGTCTGGTACCTC1486 3726381 EME1 CCACCCCCGGTCGAGGATCCTCGTG 1487 3726381 EME1TTCCACCCCCGGTCGAGGATCCTCG 1488 3726382 EME1 TCCGACACGGAACGTCACAGTGAAC1489 3726382 EME1 ACACGGAACGTCACAGTGAACCTCC 1490 3726382 EME1GCGTCCGACACGGAACGTCACAGTG 1491 3726382 EME1 CGACACGGAACGTCACAGTGAACCT1492 3726383 EME1 GTAAACACAGGTACTAGCTGTTACC 1493 3726383 EME1CCTCGGTTGTCATGACCACAACGAG 1494 3726383 EME1 TCCGTAAACACAGGTACTAGCTGTT1495 3726383 EME1 GTCATGACCACAACGAGGCCCGTCT 1496 3726384 EME1CCTTCGGACCTGTCGTGATACTTTC 1497 3726385 EME1 CTTCCTTTGCGAAGTCCCGAAACAT1498 3726385 EME1 CGTCCCTTTCGAGACAGTGACCACT 1499 3726386 EME1CAGTGAGACGTTCCATCAGGTAGAG 1500 3726386 EME1 AAAGTACAATTTTCCCCGTCGAGAA1501 3726386 EME1 CCCTACGAGACCAGGTCAGAAGAAG 1502 3726386 EME1ATAAGTAACGTCTACATCCAGTGAG 1503 3726387 EME1 GGACCTCGACGACAAGAAACTAAAG1504 3726387 EME1 AGAAACTAAAGGAGGGGACGTGGTC 1505 3726387 EME1CTCGACGACAAGAAACTAAAGGAGG 1506 3726387 EME1 CGACGACAAGAAACTAAAGGAGGGG1507 3726388 EME1 TACCATAGGTCCCATCTGCGACTTC 1508 3726388 EME1TCTCCGGTCGTATCCCAGGTACCAT 1509 3726388 EME1 AGGTACCATAGGTCCCATCTGCGAC1510 3726388 EME1 GTATCCCAGGTACCATAGGTCCCAT 1511 3726389 EME1GACCTTTCTCGACCGGCTGAAGTGT 1512 3726389 EME1 GACCGGCTGAAGTGTACGCGTAAGT1513 3726389 EME1 CGGGTCCGAGTTTAACACGTCTCGA 1514 3726389 EME1TCCGAGTTTAACACGTCTCGACCTT 1515 3726390 EME1 GTCCGACTATAGTATCCGGTCCAAT1516 3726390 EME1 ACTCCGGACTTCTCTAACTGAACAG 1517 3726390 EME1GGTATCCGGTTCAATGGTCCTAATT 1518 3726390 EME1 AAAGTCAACGGTGAACTCCCCTTGT1519 3726391 EME1 ACGTCAACACTTACGGATAGGGAGG 1520 3726391 EME1CCTGAGCGTGATCAGACCTCCTCTG 1521 3726391 EME1 TAAGTCGTCGACTTGGCTCAGTCGG1522 3726391 EME1 TCGAGGCTCTACTTTGATGGAAGAG 1523 3726392 EME1CTTGCGGTCTTAAACGAGCGTCTGT 1524 3726392 EME1 CACTGTAGGTGAAGAGCGGCGTAAC1525 3726392 EME1 CTGGTCTTGATAGGTCCGCATAGAT 1526 3726392 EME1TAGTCGTCACAAAAAGCCTATTTCT 1527 3726393 EME1 ACCGTAAATTACAAGGAGAGGACCG1528 3726393 EME1 GGTTCCTTGCCCTAATACTACTGAT 1529 3726393 EME1CTACTGATACGCCTGAAGATATAAC 1530 3726393 EME1 CTCCGGGTCAGAAAGAACCCAGAAT1531 3756194 TOP2A GCCCCTGTTGTAAACTAGGTTCTAG 1532 3756194 TOP2AACGAGTCGTTACTCGATAATCTAAG 1533 3756194 TOP2A TCTGGACAGATGTAACAATATACAC1534 3756194 TOP2A GACCTAACGTCTTCTGAGCCCCTGT 1535 3756195 TOP2ATCACTGGTAGAGTACCCGTAACAAA 1536 3756195 TOP2A AAGAGTTTAGTAGTCTCCGGCTTCT1537 3756195 TOP2A GACTAGTGAAGTCGCATTTCGTCAC 1538 3756195 TOP2ATGTGAAACCGACACAGATATTGAAC 1539 3756196 TOP2A TAGACATGCCCGTTTCTTTGGATAT1540 3756196 TOP2A GGTATACCTGAAACTGAGTCGACAC 1541 3756196 TOP2ACGAGGAGCCCGTTTTAGACATGCCC 1542 3756196 TOP2A GTTCCCCCTCTCACTACTGAAGGTA1543 3756197 TOP2A ACAAAGCTTTCGTCAGTGTTCGTTC 1544 3756197 TOP2AGACCACAGAGAGTTTTCGGACTAGG 1545 3756197 TOP2A ACGGTTTTGGTTCTTAGCGGCGTTT1546 3756197 TOP2A AGCGGCGTTTTCCTTCGGTAGGTGA 1547 3756198 TOP2ATCAAGGATTTTTCTTACACTGTCAC 1548 3756198 TOP2A CAAGGATTTTTCTTACACTGTCACT1549 3756198 TOP2A GATTTTTCTTACACTGTCACTTCTT 1550 3756198 TOP2AAGGATTTTTCTTACACTGTCACTTC 1551 3756199 TOP2A ACATGGTGACAGAAGTTCGGGAGGA1552 3756199 TOP2A CCGTCACATGGTGACAGAAGTTCGG 1553 3756199 TOP2ATTCGGGAGGACGATGTGTAAAGGGT 1554 3756199 TOP2A TCGGGAGGACGATGTGTAAAGGGTC1555 3756200 TOP2A AATCATTGTTTCTTGACTTTGGTGT 1556 3756200 TOP2ACTTTGGTGTCTTTTCACAGCACAGT 1557 3756200 TOP2A TTTGGTGTCTTTTCACAGCACAGTC1558 3756200 TOP2A ATCATTGTTTCTTGACTTTGGTGTC 1559 3756201 TOP2AACTACTTCTAAAACAGGGTAGTCTA 1560 3756202 TOP2A TGTTTGATGTAACCGTAAATTCGGT1561 3756202 TOP2A TCTCTTTAGGGACCAGACTAAGTCT 1562 3756202 TOP2ACATTAAAACTACAGGGAGGTGCTCT 1563 3756202 TOP2A AGTCTATCCTCGTCACTGCTTTCAT1564 3756203 TOP2A ACACCTTGATCTTCCGGATTTTGTT 1565 3756203 TOP2AGATCTTCCGGATTTTGTTTCTAATC 1566 3756203 TOP2A TCTACCACACCTTGATCTTCCGGAT1567 3756203 TOP2A TTTTATGACTTCCTTCGGGAGTTCT 1568 3756204 TOP2ATTGTTCTACTTGTTCAGCCTGAAGG 1569 3756204 TOP2A CCAGTTTCTCAGTAAGGTGCTTATT1570 3756204 TOP2A ACGGAAGAGGCGCACCAGTTTCTCA 1571 3756204 TOP2AAAGGTGCTTATTGGTATCTTTACTT 1572 3756206 TOP2A GGAAGTTGATAGAAGAACTATACGG1573 3756206 TOP2A ACTATACGGGGAAACCATAAATTGG 1574 3756206 TOP2AACTGAGGCATTGTCTAAGACCTGGT 1575 3756206 TOP2A GTCTAAGACCTGGTTGGAAGTTGAT1576 3756207 TOP2A TACTTCTCTCACTGTTGCTTTTCCT 1577 3756207 TOP2AACTTCTCTCACTGTTGCTTTTCCTT 1578 3756207 TOP2A TTACTTCTCTCACTGTTGCTTTTCC1579 3756207 TOP2A CTTCTCTCACTGTTGCTTTTCCTTT 1580 3756208 TOP2AAAGTCTCCCCTATACTAAGCCTAGG 1581 3756208 TOP2A AAGACTAAGTCTCCCCTATACTAAG1582 3756208 TOP2A CTATACTAAGCCTAGGACACTTCCG 1583 3756208 TOP2ATAATTAATTTCAAGACTAAGTCTCC 1584 3756209 TOP2A CTCTGAAAAAACTTGAGTCTGAATT1585 3756209 TOP2A TTAGTCCGAGCGAAATAGAATCTCT 1586 3756209 TOP2ATTACCGAGGATCCTTACGAACCACG 1587 3756209 TOP2A CGAAAAACTGGTGCATCCGACAAAT1588 3756210 TOP2A TGTTTCAGAAGTTTGAGGTTTGATC 1589 3756210 TOP2AGGAGGAGAGTATTGTCTGATATCCC 1590 3756210 TOP2A CGTCTCTCTCAACCTGATGTGTTTC1591 3756210 TOP2A CTGATATCCCTTATGGTATGTCTAT 1592 3756211 TOP2AACCGAGGTTTAGTTATACACTAATC 1593 3756211 TOP2A TGTTGGTAACTTTAGAGTCTCGAAG1594 3756211 TOP2A AGTTCCCATGATAACTTCTTGACCG 1595 3756211 TOP2AAGTCTCGAAGGGCAGTCTTGTACCT 1596 3756212 TOP2A GCACAACTCGGACTTACCATGTAAG1597 3756212 TOP2A CATGACCCACCAGGACGTTTTAGGG 1598 3756212 TOP2ACCGAGCTAACAATAAAGGTGGTTTT 1599 3756212 TOP2A GGGTTGAAACTACACGCACTTTAAC1600 3756213 TOP2A CGTTCCTAAGACGATCAGGTGCTAT 1601 3756213 TOP2ACTGGTAATAGTTAAACCGAGTCTTA 1602 3756213 TOP2A GTCGGGTAACCAGTCAAACCATGGT1603 3756213 TOP2A GGTCCGATGTACCACCGTTCCTAAG 1604 3756214 TOP2ACTTCATTTCCAACGGGTTAATCGAC 1605 3756214 TOP2A ACTGTTCGCTCTTCATTTCCAACGG1606 3756214 TOP2A ACAAATGAACGAAGTTTGCCTTACT 1607 3756214 TOP2AGTTTGCCTTACTGTTCGCTCTTCAT 1608 3756215 TOP2A AGTTTAAGACTATTGCTCTCTAGAT1609 3756215 TOP2A TCTAGATAGGGAAGATACCACCTAC 1610 3756215 TOP2AGAAGTAGTTGTTCCTTGAATAGAAC 1611 3756215 TOP2A AGACTGTATATTACTGAAGTAGTTG1612 3756216 TOP2A CTACTAGCTTTCCTTACCAATTGAT 1613 3756216 TOP2AGTTGCTTTCAATGAACCCGAAGGAC 1614 3756216 TOP2A CAATTGATTAAAGTACCTCCTATCT1615 3756216 TOP2A TTGTCTATCTACTAGCTTTCCTTAC 1616 3756217 TOP2AGGTCGTGTAGTTTCCTTCGATTTCT 1617 3756217 TOP2A CTTTTCTGTAGCATAGGTCAAGTTT1618 3756217 TOP2A CTTCGATTTCTTATGAAACGTCTAT 1619 3756217 TOP2AAGCATAGGTCAAGTTTATAAGACCA 1620 3756218 TOP2A TTCTCACCTTCTCAAGATGAGGTTT1621 3756218 TOP2A TCTCACCTTCTCAAGATGAGGTTTA 1622 3756218 TOP2ACTTCTCACCTTCTCAAGATGAGGTT 1623 3756219 TOP2A AGACGCTGTAGCAAAAGACCTCCTT1624 3756219 TOP2A ACGCTGTAGCAAAAGACCTCCTTAA 1625 3756219 TOP2AACCGGGAGAGAAGACGCTGTAGCAA 1626 3756219 TOP2A GAGAGAAGACGCTGTAGCAAAAGAC1627 3756220 TOP2A TTATAGTAGTTCTAACACCCAGAAG 1628 3756220 TOP2AGTAACTTCTGCGAAGCAATACCCTT 1629 3756220 TOP2A TTCTAACACCCAGAAGTCATGTTCT1630 3756220 TOP2A CTAAGTAACTTCTGCGAAGCAATAC 1631 3756221 TOP2AACAAGCTCTTCGAAGAGTATTCGTC 1632 3756221 TOP2A ACCCTCTCTGTTTATACCCCAAAAG1633 3756221 TOP2A TTTTATGAGTTACAAGCTCTTCGAA 1634 3756222 TOP2AACTCCCTCTAAGTCGGTTTTGAAAC 1635 3756222 TOP2A CCCTCTAAGTCGGTTTTGAAACCGA1636 3756222 TOP2A GAGGTGACTCACATGCGAATAGGAC 1637 3756222 TOP2AGCGAATAGGACTGACTCCCTCTAAG 1638 3756223 TOP2A CTTAGTTCCCTTAAGGGTTTGAGCT1639 3756223 TOP2A CAATTTGTTCTTCACAAGTCGACAT 1640 3756223 TOP2AGTAACCGACACCATAACATCTTTCG 1641 3756223 TOP2A ACATCTTTCGTATGATTTGACCCAC1642 3756224 TOP2A AACTTTTGGGTTGGAAACTGAGAGT 1643 3756224 TOP2ATTTTGTACTGAAATGTTGGGTTCTC 1644 3756224 TOP2A TTGGGTTGGAAACTGAGAGTCTGTT1645 3756224 TOP2A ACATTTACGGAATTAACTTTTGGGT 1646 3756225 TOP2AACCACAACGTCATTTTCGTGTAGTC 1647 3756225 TOP2A CTAACACTGATTTGAACAACTACAA1648 3756225 TOP2A TGTTCCCACCACAACGTCATTTTCG 1649 3756225 TOP2ACGACTAGTCTAACACTGATTTGAAC 1650 3756226 TOP2A GGTGTCCACCCTTCACACAAATTGA1651 3756226 TOP2A TTTCCTAAAGCATCAATACACCTGT 1652 3756226 TOP2AGTTCAACCTACTTTGACCATTGAGG 1653 3756226 TOP2A TCCGAAAGTCGTTTAATCGAAACAG1654 3756227 TOP2A ATATGTACATAGTGGAAAGTCGGAC 1655 3756227 TOP2AATAACGACCTAGGTGGTTTCTACAG 1656 3756227 TOP2A TTACGTTTCGGACCTGTTTCTATAA1657 3756227 TOP2A AACAACGTGATTACCAGTCTTCTCG 1658 3756228 TOP2ACCGATACCTCGGTTTAACACATTGT 1659 3756228 TOP2A CATTGTATAAGTCATGGTTTAAATG1660 3756228 TOP2A ACCGATACCTCGGTTTAACACATTG 1661 3756229 TOP2AACTTTTCTACATACAGGGTCGAGAG 1662 3756229 TOP2A AAACCTGTCGAGGATTGAAGATCAT1663 3756229 TOP2A GTCGAGGATTGAAGATCATTGATAC 1664 3756229 TOP2AGAGTATAAACCTGTCGAGGATTGAA 1665 3756230 TOP2A GAACATAATCTCAGTGTTAACTAGG1666 3756230 TOP2A CCTGGGTTTTTACAGAACATAATCT 1667 3756230 TOP2AATTACGACGCCTGTTGTTTGTTTCC 1668 3756230 TOP2A ACGCCTGTTGTTTGTTTCCCTGGGT1669 3756232 TOP2A GCGGGTCTGTGGATGTAACCAAGAC 1670 3756232 TOP2AGTGGATGTAACCAAGACACCTTAAT 1671 3756232 TOP2A ACCAAGACACCTTAATCACTGGGTC1672 3756232 TOP2A CTTGTATAAAACGAGGCGGGTCTGT 1673 3756234 TOP2AAGAACTCGGGGAAGTGCTGGCAGTG 1674 3756234 TOP2A AAGAACTCGGGGAAGTGCTGGCAGT1675 3756234 TOP2A GAACTCGGGGAAGTGCTGGCAGTGG 1676 3756234 TOP2ACAAGAACTCGGGGAAGTGCTGGCAG 1677 3756235 TOP2A CAGGACGGACAAATCAGCGAAAGTC1678 3756235 TOP2A CCCAGGACGGACAAATCAGCGAAAG 1679 3756235 TOP2AAAGTTCACCTCGAGAGGATTGGCTG 1680 3756235 TOP2A TTGGCTGCGCGCAGACACCTCTTCG1681 3756237 TOP2A AATTTATCCTTAAGTATGGTCCCTG 1682 3756237 TOP2ATTATCCTTAAGTATGGTCCCTGTTT 1683 3756237 TOP2A ATCCTTAAGTATGGTCCCTGTTTCG1684 3756237 TOP2A CCTTAAGTATGGTCCCTGTTTCGTC 1685 3757155 KRT14ACCGTTAGTTATGTCGAAGTAATAG 1686 3757155 KRT14 ATCCTCCGGGGGGCACACCTGTGTC1687 3757156 KRT14 GCGGTTTAGGCGTGGTTCCAGTACC 1688 3757156 KRT14TCGGCGGTTTAGGCGTGGTTCCAGT 1689 3757156 KRT14 CGGTTTAGGCGTGGTTCCAGTACCT1690 3757156 KRT14 AGGTCGGCGGTTTAGGCGTGGTTCC 1691 3757157 KRT14ACCCTCGGGAGCAGACTTTCTTTAC 1692 3757157 KRT14 ACTCGAGATCACGACAGTGGGTCAA1693 3757157 KRT14 GAGAACGAAGATGCACCACAGACAC 1694 3757157 KRT14GACTCTGGTGAGGTAACCCACTTAT 1695 3757160 KRT14 GACCTCCTCTGGTTTCCAGCGATGA1696 3757160 KRT14 TCTAGGTCCTCTACTAACCGTCGCA 1697 3757160 KRT14TCCTCTGGTTTCCAGCGATGACGTA 1698 3757160 KRT14 CTGGTTTCCAGCGATGACGTACGTC1699 3757162 KRT14 GTTCTCGCTCTAGAGCCTCGAGGCC 1700 3757162 KRT14CGTCTTGGACCTCTAACTCGACGTC 1701 3757162 KRT14 ACCGGTGGTTGTCGCTCGACCACGT1702 3757162 KRT14 CCTCGAGGCCGCGTGGTACGTCTTG 1703 3757164 KRT14CCTCTACCTGCGACGTGGACCGCAC 1704 3757164 KRT14 CGGTCCACCCACCTCTACAGTTACA1705 3757164 KRT14 CTACTTACGGGACTCTCCGGTCCAC 1706 3757164 KRT14AGACTTGCTCTACGCACTGGTCATA 1707 3757167 KRT14 CACAGAGTATGGAAAAGAGACCCCA1708 3757167 KRT14 CTACCCACAGAGTATGGAAAAGAGA 1709 3757167 KRT14ATGGAAAAGAGACCCCAGTAAGGTC 1710 3757167 KRT14 AGTATGGAAAAGAGACCCCAGTAAG1711 3757169 KRT14 TCGGTGTCACCTGTTACGGTTACAG 1712 3757169 KRT14ACTGTTACGGGCAGACCGGCGCCTA 1713 3757169 KRT14 ACCGGCGCCTACTGAAGGCGTGGTT1714 3757169 KRT14 CGGTTACAGGAAGACGTCTAACTGT 1715 3757172 KRT14ACCCCCTCCTATACCACCACCGGAA 1716 3757172 KRT14 CCGAAACCACCACCGAAACGACCAC1717 3757172 KRT14 ACCGGAACCACGACCGAACCCACCA 1718 3757172 KRT14GAAACGACCACCACTACCCGAAGAC 1719 3757174 KRT14 TGAGTCGGTTGACGAGCGAGCGAGT1720 3757174 KRT14 AAGAGAAGTGAGTCGGTTGACGAGC 1721 3757174 KRT14AAGTGAGTCGGTTGACGAGCGAGCG 1722 3757174 KRT14 TGGGCTCGTGGAAGAGAAGTGAGTC1723 3757199 KRT14 CTCTTCCACTGGTACGTCTTGGAGT 1724 3757199 KRT14CACTGGTACGTCTTGGAGTTACTGG 1725 3757199 KRT14 TTCCACTGGTACGTCTTGGAGTTAC1726 3757199 KRT14 CGTCTTGGAGTTACTGGCGGACCGG 1727 3815758 MUM1CGTCGCCAACCGCCCGCCCAGGAGG 1728 3815758 MUM1 GACGCCGGAGGAACGGGCCCGAACC1729 3815758 MUM1 GCCCAGGAGGCGACAACGCCGGCGA 1730 3815758 MUM1CCGCCGCGCCTGCCGTCGCCAACCG 1731 3815759 MUM1 ACTCTGGACCCTCATGCAACACGGT1732 3815759 MUM1 TGTGTAACCGCACTCTGGACCCTCA 1733 3815759 MUM1TGTAACCGCACTCTGGACCCTCATG 1734 3815759 MUM1 CCTCATGCAACACGGTTTAGTAACG1735 3815762 MUM1 ACCGGGCTTGGCGCTGAAGTTGTTT 1736 3815762 MUM1ACACGTTTAGGAGAGAGATCTCCTT 1737 3815762 MUM1 TTCCTTATAAAAGATCGACACGTTT1738 3815762 MUM1 AAACCGGGCTTGGCGCTGAAGTTGT 1739 3815763 MUM1TGTCAACTTCGGGTCGGGTGAGAAT 1740 3815763 MUM1 AAGGGCACATCTAAAGACTATGAAG1741 3815763 MUM1 CAAAGAATTAGTCACGGTACGGTCC 1742 3815763 MUM1GGTTTGCTCCGTAAGACACTCTAGA 1743 3815764 MUM1 TTCCGTTTATTGACTACTGGTCCGC1744 3815764 MUM1 TGCAGACACTGTCCGGGTAGTTAAA 1745 3815764 MUM1TGGTCCGCCGTGTAACAAGACGAGG 1746 3815764 MUM1 CGGACAGTGAGATTTGGTCGCAAAT1747 3815765 MUM1 CCACGTAGACAGCACTCTTAAGGGT 1748 3815765 MUM1CGTGGCCCTTCCACATCTAGTAGAT 1749 3815765 MUM1 ACTAGGGCGCATCAGGTTCCGTAAC1750 3815765 MUM1 TCGACGGAGACTTCGAGCGAACCAG 1751 3815766 MUM1GAGTGTGAAAGGGACGCCGACCCTT 1752 3815766 MUM1 AGTGTGAAAGGGACGCCGACCCTTC1753 3815767 MUM1 CATTGGAGTCCGTCTACTTAAGGAT 1754 3815767 MUM1TGGTCCCAAGAACGACGGACATTGG 1755 3815767 MUM1 ACTTTTACAGAACCGCCGCAACCGA1756 3815767 MUM1 CACATTGCAGCTAAAACAGAGACGT 1757 3815769 MUM1TTGCGCTTAGGGGACTCGACTTCCT 1758 3815769 MUM1 ATAAGAACTGCGGGTCTTACCAGTC1759 3815769 MUM1 CTTAAACGGGGATCTTGGTGAGGAT 1760 3815769 MUM1TGAGGATAAGAACTGCGGGTCTTAC 1761 3815770 MUM1 GAGACGTATTGAATCCGGCCCGACT1762 3815770 MUM1 TAGTAGAACCTACCGCAGCAGGAAC 1763 3815770 MUM1CCGTGGGTAACAAACTCCGTGACAG 1764 3815770 MUM1 CGTAATACGGGCGACTCAACACTAT1765 3815771 MUM1 TGTCTGCCAGCGAAGCGCACCGAGA 1766 3815771 MUM1CCAAGGACGCCGTGGGGACCTTCTT 1767 3815771 MUM1 CTTGACCGGATGTCTGCCAGCGAAG1768 3815771 MUM1 GAGACCTGCAAGACTCGCTCCCGAG 1769 3815772 MUM1CGGTACACACGTTGTTTCGGACAGT 1770 3815772 MUM1 GGTCTACAGAAGGAACGGGCCTAAG1771 3815772 MUM1 CAACCCGTCAAGGTCTGGAGTGTCC 1772 3815772 MUM1CTCGTACAGAGGAGCGGGACACTAA 1773 3815773 MUM1 TCTCAGGTACCCCAGATTAAGGTAC1774 3815773 MUM1 CCTTCTGCTCCTCGGTGGTTCTCAG 1775 3815773 MUM1ACGGTCAGAAGGCTTCTCAGGTACC 1776 3815773 MUM1 CCCCAGATTAAGGTACGCAAGATAG1777 3815774 MUM1 CCTTACGATCAGACCGTATTTGTAT 1778 3815774 MUM1ACTTCATCCTTACGATCAGACCGTA 1779 3815774 MUM1 CATCCTTACGATCAGACCGTATTTG1780 3815774 MUM1 ATCCTTACGATCAGACCGTATTTGT 1781 3815775 MUM1TTTCGCAGTCCGTCTCTCTATTCTT 1782 3815775 MUM1 CAGTTTTCGCAGTCCGTCTCTCTAT1783 3815775 MUM1 TCGTTCACACGATATGTAGCTTCCT 1784 3815775 MUM1TCCTGTGTACTTGGGCTTTTACTTT 1785 3815778 MUM1 CCGACCACACAGAGGGAGTAGTGGC1786 3815778 MUM1 TTCGGTCCCTCCTGAAGTTGGTCCT 1787 3815778 MUM1GTAGTGGCTGATGTCCCAGGCCAAT 1788 3815778 MUM1 CCTGAAGTTGGTCCTGTAGCCGACC1789 3815780 MUM1 GGCTTTTAGGTAGGTCGTCCTGCAG 1790 3815780 MUM1AACCCCTGGTTCGAAGGAGTTGACT 1791 3815780 MUM1 CGAAGGAGTTGACTCGTTCCCCTCG1792 3815780 MUM1 GAACCCCTGGTTCGAAGGAGTTGAC 1793 3815781 MUM1GTGGACGCCCGGTAGGATTTCTCGT 1794 3815781 MUM1 ACTTCATGGACGTCCCGCAGATGGT1795 3815781 MUM1 AGTAAGACCTGCACGAAGACGGGCT 1796 3815781 MUM1ACTCGAGGTCGGTCATGCACTGGAC 1797 3815783 MUM1 ACGAACAGTGTCGATTCCCACGAAG1798 3815783 MUM1 CTCTGAGACGAGACTTGGCTTACCT 1799 3815783 MUM1AAGAATTGGCGTCCGGTGAACCCCG 1800 3815783 MUM1 GTCCCTAAGTACCTGATCCAAACGT1801 3815784 MUM1 ACCTGCTCCACCTGATGTTCTGCCG 1802 3815784 MUM1GTAGTTCCCCGGAAGCGACTCGATG 1803 3815784 MUM1 TTCTGCCGACTCCTCTTCATGTAGT1804 3815784 MUM1 CGGTAGTAGACACGCTAGAGACGCC 1805 3815786 MUM1CCGGGTCGACCGAATGGTTTTGTCC 1806 3815786 MUM1 CTCGCGGATTAGGACAGAGACCCGT1807 3815786 MUM1 AAAGGACGACCTAGAAGTACCAAGG 1808 3815786 MUM1TGTAGGCACACGAATCGACGGGAAC 1809 3815787 MUM1 GGGCAATCCTCAAGTAGTGTCGAAG1810 3815787 MUM1 AACGGCTGTAGTTTTGGGCAATCCT 1811 3815787 MUM1GCGGCCCCTGTACGAGTTTTATTGT 1812 3815787 MUM1 GGTCAACGGTACTTTCGGAGGGCAC1813 3815790 MUM1 CTTTATAAACTGTTGGTCGAGGAAC 1814 3815790 MUM1TCTTTATAAACTGTTGGTCGAGGAA 1815 3815790 MUM1 CGAGGAACTTCTCGCCTTGGCCGCG1816 3815790 MUM1 AACTTCTCGCCTTGGCCGCGGCAGC 1817 3815791 MUM1GACCGCCACCTTCGCGGAGGTCACA 1818 3815791 MUM1 GGACCGCCACCTTCGCGGAGGTCAC1819 3815791 MUM1 CGGACCGCCACCTTCGCGGAGGTCA 1820 3815791 MUM1CCGCCACCTTCGCGGAGGTCACACG 1821 3815792 MUM1 CCTCTTAGGTAAAGCAATTGTGACT1822 3815792 MUM1 CGACACCAAAGAGGGCTGCACGTGT 1823 3815792 MUM1CTTCGCATAAGTGACACGCGGTCAT 1824 3815792 MUM1 CTAGAGCATACACACCGTAGACTAT1825 3815793 MUM1 GGCGGACGCTGTCAAGGTCTTAAAC 1826 3815793 MUM1TCTTAAACGAGAGGGTGAGTCACAC 1827 3815793 MUM1 TCAGTGGCGCCAGAGTCAGTAGCCG1828 3815793 MUM1 GCGTCGGAAACATACCTCCGGGTTG 1829 3815794 MUM1AAACTCCCCGACACTGGGAGAAGGG 1830 3815794 MUM1 TACAGGTCCCAAGGTCCCGGGCCAC1831 3815794 MUM1 ACGAAACTCCCCGACACTGGGAGAA 1832 3815794 MUM1CGGAACGAAACTCCCCGACACTGGG 1833 3815795 MUM1 GTCGGCTGCTGTCGGTGGCCTCTCC1834 3815795 MUM1 CTCCTCTAGCCTTGTGCTAACAGAG 1835 3815795 MUM1TTCCTGAGAGCATAGCCCGGGAACC 1836 3815795 MUM1 CCTGCTTCGGCGTTCCTGAGAGCAT1837 3815796 MUM1 GTCCTTTGGGCCGGCACCGGACCGT 1838 3815796 MUM1ACTGGAAACAAAGTGAACGGAGACG 1839 3815796 MUM1 GAGCTGAGGCTCTCGTCCTTTGGGC1840 3815796 MUM1 TGAACGGAGACGAGCTGAGGCTCTC 1841 3815797 MUM1CGCCCCGAGTCGTCGCAACGTACAT 1842 3815797 MUM1 GCCGGTCATGGTGGCGGACTCCGCC1843 3815797 MUM1 GGGACGACCAGCGACAAAGCCCCTG 1844 3815797 MUM1CCTCGTCACCCCGTGTGGGGCCTCC 1845 3815798 MUM1 AGTACCTTTTAGGAGGCCTCGGCGG1846 3815798 MUM1 GCCCGGAGCATGACGGAGTACCTTT 1847 3815798 MUM1ACGGAGTACCTTTTAGGAGGCCTCG 1848 3815798 MUM1 AGCATGACGGAGTACCTTTTAGGAG1849 3815799 MUM1 GGAACGGTTCAACAAGCTCCACCTT 1850 3815799 MUM1CTCCACCTTAATTTGTGGAGGGTCT 1851 3815799 MUM1 CTCATCCTGTGTAACGGTACCAAAA1852 3815799 MUM1 GACGACAACACTTCATGAAAATAGG 1853 3908359 SULF2TAAGCGGAACCGGTTGGGAAGAAAC 1854 3908359 SULF2 GATCGTTGAGGGATCACCGCAAAAA1855 3908359 SULF2 AAATTGTCTACTGCCTCTATTAGGG 1856 3908359 SULF2GGGAAGAAACACATAGTCCATCAGA 1857 3908360 SULF2 CCTCATCTACCAACATCTAACTGAT1858 3908360 SULF2 TATGATGGTCAGTTGTAGAAAAACC 1859 3908360 SULF2AGATGGTATGAAGTTCCCTGATGTC 1860 3908360 SULF2 TAAGTTCTATGATGGTCAGTTGTAG1861 3908361 SULF2 CGGTTACTGGTCGTCAACCATACTT 1862 3908361 SULF2AGAAACAATACAGGGTCTTGACTAC 1863 3908361 SULF2 AGGGAGCGTCAACACCTGTAAAGAC1864 3908361 SULF2 ACAGGTCTATGGTAAAGAGGATCAT 1865 3908362 SULF2AAACCTAATATGGAGTGGTCGACGT 1866 3908362 SULF2 AGAGGGTTCCCGCTTTCAGTAACCT1867 3908362 SULF2 TCGTCAGGACAAGATTTAGGAGAAT 1868 3908362 SULF2ACCACAGTTATTTGCGAGACACCGG 1869 3908364 SULF2 TCAAAGTCGCAGCTTTCACCGGTCT1870 3908364 SULF2 CAAAGTCGCAGCTTTCACCGGTCTT 1871 3908364 SULF2CGTCAAAGTCGCAGCTTTCACCGGT 1872 3908364 SULF2 AAAGTCGCAGCTTTCACCGGTCTTT1873 3908365 SULF2 GACGTGGACAATAGAACTCTTTGAC 1874 3908365 SULF2TCAGAGTAGAGACACTCAGACGTGG 1875 3908365 SULF2 GTCCTAGTGGGTGGTTTCTATCCAC1876 3908365 SULF2 CCACAGTGGATCCTCTGGAAGAAAC 1877 3908366 SULF2TACCTCCTTCGATACTCGTTATGTC 1878 3908368 SULF2 GGACTTTGGTACAACTGATTTCTAC1879 3908368 SULF2 ACGGGTCCTTTGTGTGCCTTAAGGC 1880 3908368 SULF2GCCTTAAGGCAGAGTAAAGTAACAG 1881 3908368 SULF2 CTCTCTCCTTGTGGACGTGGTTGAC1882 3908369 SULF2 CTACAGGAGTTGGTCGATGTGCATG 1883 3908369 SULF2GTTGGTCGATGTGCATGTCGAGTAC 1884 3908369 SULF2 GGGGCCTGAGCTTTGTACCTGGACC1885 3908369 SULF2 GGTCGATGTGCATGTCGAGTACCTC 1886 3908371 SULF2ATCTCATGAAACTAGAGTTGTGTCT 1887 3908371 SULF2 GGTCGCGGTTGTTATTGTGCATGAC1888 3908371 SULF2 ACGTACTCCTGGTAGTTACTCTGAG 1889 3908371 SULF2CACTTAAACGTTGACCGAAGGATCT 1890 3908373 SULF2 GTCCGGAGTGCACGAAGTGGGTGCT1891 3908373 SULF2 AGTGCACGAAGTGGGTGCTGTTGGT 1892 3908373 SULF2ACCGTCTGCCGCGGAAAGACCTGTG 1893 3908373 SULF2 TGCTGTTGGTCGTGACCGTCTGCCG1894 3908374 SULF2 AGTTCGCGGACGTCTTGTTGCTGTG 1895 3908374 SULF2ACGAGTTCGCGGACGTCTTGTTGCT 1896 3908374 SULF2 GACGAGTTCGCGGACGTCTTGTTGC1897 3908374 SULF2 GGACGTCTTGTTGCTGTGCACGTCG 1898 3908375 SULF2ACCGACAACGCCCTCGTCTTCGCGT 1899 3908375 SULF2 ACAACGCCCTCGTCTTCGCGTTCTT1900 3908375 SULF2 GACAACGCCCTCGTCTTCGCGTTCT 1901 3908375 SULF2CCACACCGACAACGCCCTCGTCTTC 1902 3908377 SULF2 TCTCCGAGGTCAGACGTAGGAAAGT1903 3908377 SULF2 GTGTTTCCGGCGGAGTTCGTGTCTC 1904 3908377 SULF2CTCCGAGGTCAGACGTAGGAAAGTC 1905 3908377 SULF2 TGTTTCCGGCGGAGTTCGTGTCTCC1906 3908381 SULF2 CTTTTTCGCCGGTCTTCTTACACTG 1907 3908381 SULF2TCGCCGGTCTTCTTACACTGACAGT 1908 3908381 SULF2 TTCGCCGGTCTTCTTACACTGACAG1909 3908381 SULF2 CCGGTCTTCTTACACTGACAGTGTT 1910 3908382 SULF2GTCTTGTTTTAATTCTTGGACTCCC 1911 3908382 SULF2 TAATTCTTGGACTCCCTTCAGGCTC1912 3908382 SULF2 GACGTCTTGTTTTAATTCTTGGACT 1913 3908382 SULF2GGGACGTCTTGTTTTAATTCTTGGA 1914 3908388 SULF2 GACCTGGACATGTTCAGGGACGTCC1915 3908388 SULF2 GGATCTCTTGCTGTGTCAGGTCACA 1916 3908388 SULF2GGTCACACTGGACCTGGACATGTTC 1917 3908388 SULF2 AGGATCTCTTGCTGTGTCAGGTCAC1918 3908390 SULF2 GTCAGCGAGGTAGGCGAGTCACCGG 1919 3908390 SULF2TGTTCCGGTCGATACAGGCGTCAGC 1920 3908390 SULF2 GCTTTGGAGTGGTTCGCCGTGACCG1921 3908390 SULF2 TGCCGTCCCACATGGTGCATCCGGA 1922 3908391 SULF2GCCCCTGATGTTCGAGTCGGACCGG 1923 3908391 SULF2 GACGTGGACACTGTCGCCCCTGATG1924 3908391 SULF2 GTTGGAGCACGGGTTCATGATGCCC 1925 3908391 SULF2TCGACTTCGACGTATTCACGTTCCC 1926 3908393 SULF2 GACTCATGGTCTGCCGCACACTCGT1927 3908393 SULF2 TGGACACAGTCGCACGACTCATGGT 1928 3908393 SULF2TGGTCGCACACTTCCTGGACACAGT 1929 3908393 SULF2 CTGCGGGTCCTCCTCTTGAAAGACG1930 3908394 SULF2 TCCCAGACCGCCCTGAGGAAGAACC 1931 3908394 SULF2TTCTACTCCCAGACCGCCCTGAGGA 1932 3908394 SULF2 TACTCCCAGACCGCCCTGAGGAAGA1933 3908394 SULF2 ACTCCCAGACCGCCCTGAGGAAGAA 1934 3908395 SULF2CCTGCCCTTTAGGTAGGAGTTCGAC 1935 3908395 SULF2 TGTAGCAGGAGTTGTAACTGGACCG1936 3908395 SULF2 ATGGACGCCTATACCTGCCCTTTAG 1937 3908395 SULF2CTGTAACGTCCGGACCTGTATGGAC 1938 3908397 SULF2 ACTCAAACTGTAGTCCCAGGGCAAG1939 3908397 SULF2 TGTGCATGTAGCATATGTGGCGGCT 1940 3908397 SULF2GTGCCAATGGTGTAGCCGGTCAAAC 1941 3908397 SULF2 GCCCGCTCGACCTGTTGTGCATGTA1942 3908400 SULF2 ACAGCCACCTGCTGAGGTACCTCTG 1943 3908400 SULF2GGTTGTACGAGGTCGCCTTCGCGAA 1944 3908400 SULF2 CTTCGCGAACGTCTGGGAGTACAGC1945 3908400 SULF2 TTGTGACCTAGTACGCGATGTGCCC 1946 3908401 SULF2TGCAGGTTCTTCTACATGGGCGTGT 1947 3908401 SULF2 TCTGGAGTAGTGGTTACTGTCGCAC1948 3908401 SULF2 AGGAGTACCAGTAGTCGGTACGTCG 1949 3908401 SULF2ACTGTCGCACTCGAAGAAGGCGTGC 1950 3908407 SULF2 ACCTGGATTGGTCCGGGAGGTAAAC1951 3908407 SULF2 GTGACGTGAGACTACTTAGACCACT 1952 3908407 SULF2CACACTGTCTGAAGGGTGACTACGT 1953 3908407 SULF2 CCGAAGGACTGATTTGAGGTCTCAC1954 3908417 SULF2 CCGTGTCGTGCTCTCGGCGTGGAAA 1955 3908417 SULF2CGCGTGAAGTAGTTGCGGAAGCACT 1956 3908417 SULF2 CCACTACTTGTTCTGGGCCGCGTAG1957 3908417 SULF2 GCGTGGAAACGGCACATGGAGTTAT 1958 3908426 SULF2TTCGAGCCGGAAGGACAGCGTGGTG 1959 3908426 SULF2 AGCGTGGTGGCGGACTTTCCGTCCA1960 3908426 SULF2 AACGACAGGCGTTGACACAAGAGGG 1961 3908426 SULF2GTCCAAAGTCTCCCTGGCGTCCTTG 1962 3908435 SULF2 CGCCTCAGGGGACGCGGGTCGCCGG1963 3908435 SULF2 CAGGGGACGCGGGTCGCCGGGCCGG 1964 3908435 SULF2GGGGACGCGGGTCGCCGGGCCGGCC 1965 3908435 SULF2 CTCAGGGGACGCGGGTCGCCGGGCC1966 3908436 SULF2 GCCTCCGTAGCCCTCCAGCTCTCGG 1967 3908436 SULF2GCGCCGGTCGGCTCAGGCCTCCGTA 1968 3908436 SULF2 CAAGTGACGGGGCAGGCCTCGACCT1969 3908436 SULF2 ACACGCAGACACACAGGGCCGCTCC 1970 3908437 SULF2TGTGCACGTGTGTTCCGAGACCGAG 1971 3908437 SULF2 CTACCGGGAGGACTTAAATAGTGCT1972 3908437 SULF2 CTAAGTGCAGCAAAGGTCGGTTCAC 1973 3908437 SULF2CCGCGGCCGGAGAGGTTACCGTTTA 1974 3978625 APEX2 CGACCCTCCACAAGGTCGGGAAATT1975 3978625 APEX2 CCGCGCCCGACCCTCCACAAGGTCG 1976 3978625 APEX2GACCCTCCACAAGGTCGGGAAATTC 1977 3978625 APEX2 CAACCGCGCCCGACCCTCCACAAGG1978 3978626 APEX2 CGACCTACGCCTATAGCAGACAGAG 1979 3978626 APEX2TCGACCTTGTAGTTACCCTAAGCCT 1980 3978626 APEX2 CCGCGTAAAACCTGCTCGACCTACG1981 3978626 APEX2 TAGTCCTTGGGTCGTTGACACGGCG 1982 3978629 APEX2GACATTCCTGTTACGATGGGGTCAC 1983 3978629 APEX2 TCCTTGAGGCCCGAGACCTATCACT1984 3978629 APEX2 ATACCTTTGTACCTACTCAAATGGG 1985 3978629 APEX2CCGGACTCACCGGACAAACGGTGGG 1986 3978630 APEX2 CGCGAAGATAGCAAACGACGTTTAG1987 3978630 APEX2 ATTCCTCTTCTGGAACTGGGATTAG 1988 3978630 APEX2GGACTCGCCGATCAGAAATTCTACG 1989 3978630 APEX2 CGTTTAGGCTCGTCTTCGGGAGGAC1990 3978634 APEX2 ACCTACCTGTCGAACGAGTCATTGA 1991 3978634 APEX2ACGGAGAGTACATCCCGGGAAGTAG 1992 3978634 APEX2 TATCGATGGCGACGAAGGTTGGTTT1993 3978634 APEX2 ACGAGTCATTGAACCCCACGGTCAG 1994 3978635 APEX2GAGACACGGACGTTTTGTCACGGGT 1995 3978635 APEX2 CCCCTGTCCTGGGACCAGTATCTGT1996 3978635 APEX2 GTAGAGTTGATACCGAGGGCCGAAC 1997 3978635 APEX2TCCGTGGGTCGAGTTCTAGGAAGCG 1998 3978636 APEX2 CTCGACGGATCGGATGGTGACTACT1999 3978636 APEX2 AGTTTGGGCCCATGTCTGTACGGTT 2000 3978636 APEX2GTTTCAGGACACAACCTCGTCAGCT 2001 3978636 APEX2 CGGGTCAGTCCAACCGAGATCGTCT2002 3978637 APEX2 ACTCTTCCTCAATGCCTGGAGTAAG 2003 3978637 APEX2ACTTCTTCGGTCCTGGGTTGAACCC 2004 3978637 APEX2 CTCGGTACACACTACGCATGACACT2005 3978637 APEX2 GAACCCGGCGGCGAAGATGTACACA 2006 3978638 APEX2AGGAACAACCACTCGAAGAACACGG 2007 3978638 APEX2 AACACGGAATTAGGACACTGGGTCG2008 3978638 APEX2 GGCTTCATGTGCCTGTGATCGACGG 2009 3978638 APEX2GGACGTGTACTAGACTCCGGTCGAG 2010 3978639 APEX2 ATGAGGTATTTCAACTCAGTCTCTT2011 3978639 APEX2 ACCTCCATGAGGTATTTCAACTCAG 2012 3978639 APEX2ACCTGTAACACCTCCATGAGGTATT 2013 3978639 APEX2 GTGAAACCTGTAACACCTCCATGAG2014 3978641 APEX2 GACACTGGACCTTTCACCCTCGTAA 2015 3978641 APEX2AACTTTTACCCTGACCATCTGGTCC 2016 3978641 APEX2 ACCCTCGTAACGAAACTTGTGTCAC2017 3978641 APEX2 TGTGTCACGAACGAGATCGGTTCGG 2018 3978642 APEX2GTGACACATCAAAAACCCGTAAAGG 2019 3978642 APEX2 GATCGAGAAACGTTGAGTGACACAT2020 3978642 APEX2 GTCACTTCGCAGTTAGGGACCTAAA 2021 3978642 APEX2CGTGAACAGACAAGGGACAGGTTAT

Probes/Primers

The present invention provides for a probe set for predicting responseof a subject to post-operative radiation therapy for prostate cancercomprising a plurality of probes, wherein (i) the probes in the set arecapable of detecting an expression level of at least one target selectedfrom Table 1 or Table 2; and (ii) the expression level determineswhether or not the subject will benefit from post-operative radiationtherapy with at least about 40% specificity.

The probe set may comprise one or more polynucleotide probes. Individualpolynucleotide probes comprise a nucleotide sequence derived from thenucleotide sequence of the target sequences or complementary sequencesthereof. The nucleotide sequence of the polynucleotide probe is designedsuch that it corresponds to, or is complementary to the targetsequences. The polynucleotide probe can specifically hybridize undereither stringent or lowered stringency hybridization conditions to aregion of the target sequences, to the complement thereof, or to anucleic acid sequence (such as a cDNA) derived therefrom.

The selection of the polynucleotide probe sequences and determination oftheir uniqueness may be carried out in silico using techniques known inthe art, for example, based on a BLASTN search of the polynucleotidesequence in question against gene sequence databases, such as the HumanGenome Sequence, UniGene, dbEST or the non-redundant database at NCBI.In one embodiment of the invention, the polynucleotide probe iscomplementary to a region of a target mRNA derived from a targetsequence in the probe set. Computer programs can also be employed toselect probe sequences that may not cross hybridize or may not hybridizenon-specifically.

In some instances, microarray hybridization of RNA, extracted fromprostate cancer tissue samples and amplified, may yield a dataset thatis then summarized and normalized by the fRMA technique. After removal(or filtration) of cross-hybridizing PSRs, and PSRs containing less than, the remaining PSRs can be used in further analysis. Following fRMA andfiltration, the data can be decomposed into its principal components andan analysis of variance model is used to determine the extent to which abatch effect remains present in the first 10 principal components.

These remaining PSRs can then be subjected to filtration by a T-testbetween CR (clinical recurrence) and non-CR samples. Using a p-valuecut-off of 0.01, the remaining features (e.g., PSRs) can be furtherrefined. Feature selection can be performed by regularized logisticregression using the elastic-net penalty. The regularized regression maybe bootstrapped over 1000 times using all training data; with eachiteration of bootstrapping, features that have non-zero co-efficientfollowing 3-fold cross validation can be tabulated. In some instances,features that were selected in at least 25% of the total runs were usedfor model building.

The polynucleotide probes of the present invention may range in lengthfrom about 15 nucleotides to the full length of the coding target ornon-coding target. In one embodiment of the invention, thepolynucleotide probes are at least about 15 nucleotides in length. Inanother embodiment, the polynucleotide probes are at least about 20nucleotides in length. In a further embodiment, the polynucleotideprobes are at least about 25 nucleotides in length. In anotherembodiment, the polynucleotide probes are between about 15 nucleotidesand about 500 nucleotides in length. In other embodiments, thepolynucleotide probes are between about 15 nucleotides and about 450nucleotides, about 15 nucleotides and about 400 nucleotides, about 15nucleotides and about 350 nucleotides, about 15 nucleotides and about300 nucleotides, about 15 nucleotides and about 250 nucleotides, about15 nucleotides and about 200 nucleotides in length. In some embodiments,the probes are at least 15 nucleotides in length. In some embodiments,the probes are at least 15 nucleotides in length. In some embodiments,the probes are at least 20 nucleotides, at least 25 nucleotides, atleast 50 nucleotides, at least 75 nucleotides, at least 100 nucleotides,at least 125 nucleotides, at least 150 nucleotides, at least 200nucleotides, at least 225 nucleotides, at least 250 nucleotides, atleast 275 nucleotides, at least 300 nucleotides, at least 325nucleotides, at least 350 nucleotides, at least 375 nucleotides inlength.

The polynucleotide probes of a probe set can comprise RNA, DNA, RNA orDNA mimetics, or combinations thereof, and can be single-stranded ordouble-stranded. Thus the polynucleotide probes can be composed ofnaturally-occurring nucleobases, sugars and covalent internucleoside(backbone) linkages as well as polynucleotide probes havingnon-naturally-occurring portions which function similarly. Such modifiedor substituted polynucleotide probes may provide desirable propertiessuch as, for example, enhanced affinity for a target gene and increasedstability. The probe set may comprise a coding target and/or anon-coding target. Preferably, the probe set comprises a combination ofa coding target and non-coding target.

In some embodiments, the probe set comprise a plurality of targetsequences that hybridize to at least about 5 coding targets and/ornon-coding targets selected from Table 1 or Table 2. Alternatively, theprobe set comprise a plurality of target sequences that hybridize to atleast about 10 coding targets and/or non-coding targets selected fromTable 1 or Table 2. In some embodiments, the probe set comprise aplurality of target sequences that hybridize to at least about 15 codingtargets and/or non-coding targets selected from Table 1 or Table 2. Insome embodiments, the probe set comprise a plurality of target sequencesthat hybridize to at least about 20 coding targets and/or non-codingtargets selected from Table 1 or Table 2. In some embodiments, the probeset comprise a plurality of target sequences that hybridize to at leastabout 24 coding targets and/or non-coding targets selected from Table 1or Table 2.

The system of the present invention further provides for primers andprimer pairs capable of amplifying target sequences defined by the probeset, or fragments or subsequences or complements thereof. The nucleotidesequences of the probe set may be provided in computer-readable mediafor in silico applications and as a basis for the design of appropriateprimers for amplification of one or more target sequences of the probeset.

Primers based on the nucleotide sequences of target sequences can bedesigned for use in amplification of the target sequences. For use inamplification reactions such as PCR, a pair of primers can be used. Theexact composition of the primer sequences is not critical to theinvention, but for most applications the primers may hybridize tospecific sequences of the probe set under stringent conditions,particularly under conditions of high stringency, as known in the art.The pairs of primers are usually chosen so as to generate anamplification product of at least about 50 nucleotides, more usually atleast about 100 nucleotides. Algorithms for the selection of primersequences are generally known, and are available in commercial softwarepackages. These primers may be used in standard quantitative orqualitative PCR-based assays to assess transcript expression levels ofRNAs defined by the probe set. Alternatively, these primers may be usedin combination with probes, such as molecular beacons in amplificationsusing real-time PCR.

In one embodiment, the primers or primer pairs, when used in anamplification reaction, specifically amplify at least a portion of anucleic acid sequence of a target selected from Table 2 (or subgroupsthereof as set forth herein), an RNA form thereof, or a complement toeither thereof.

A label can optionally be attached to or incorporated into a probe orprimer polynucleotide to allow detection and/or quantitation of a targetpolynucleotide representing the target sequence of interest. The targetpolynucleotide may be the expressed target sequence RNA itself, a cDNAcopy thereof, or an amplification product derived therefrom, and may bethe positive or negative strand, so long as it can be specificallydetected in the assay being used. Similarly, an antibody may be labeled.

In certain multiplex formats, labels used for detecting differenttargets may be distinguishable. The label can be attached directly(e.g., via covalent linkage) or indirectly, e.g., via a bridgingmolecule or series of molecules (e.g., a molecule or complex that canbind to an assay component, or via members of a binding pair that can beincorporated into assay components, e.g. biotin-avidin or streptavidin).Many labels are commercially available in activated forms which canreadily be used for such conjugation (for example through amineacylation), or labels may be attached through known or determinableconjugation schemes, many of which are known in the art.

Labels useful in the invention described herein include any substancewhich can be detected when bound to or incorporated into the biomoleculeof interest. Any effective detection method can be used, includingoptical, spectroscopic, electrical, piezoelectrical, magnetic, Ramanscattering, surface plasmon resonance, colorimetric, calorimetric, etc.A label is typically selected from a chromophore, a lumiphore, afluorophore, one member of a quenching system, a chromogen, a hapten, anantigen, a magnetic particle, a material exhibiting nonlinear optics, asemiconductor nanocrystal, a metal nanoparticle, an enzyme, an antibodyor binding portion or equivalent thereof, an aptamer, and one member ofa binding pair, and combinations thereof. Quenching schemes may be used,wherein a quencher and a fluorophore as members of a quenching pair maybe used on a probe, such that a change in optical parameters occurs uponbinding to the target introduce or quench the signal from thefluorophore. One example of such a system is a molecular beacon.Suitable quencher/fluorophore systems are known in the art. The labelmay be bound through a variety of intermediate linkages. For example, apolynucleotide may comprise a biotin-binding species, and an opticallydetectable label may be conjugated to biotin and then bound to thelabeled polynucleotide. Similarly, a polynucleotide sensor may comprisean immunological species such as an antibody or fragment, and asecondary antibody containing an optically detectable label may beadded.

Chromophores useful in the methods described herein include anysubstance which can absorb energy and emit light. For multiplexedassays, a plurality of different signaling chromophores can be used withdetectably different emission spectra. The chromophore can be alumophore or a fluorophore. Typical fluorophores include fluorescentdyes, semiconductor nanocrystals, lanthanide chelates,polynucleotide-specific dyes and green fluorescent protein.

In some embodiments, polynucleotides of the invention comprise at least20 consecutive bases of the nucleic acid sequence of a target selectedfrom Table 1 or Table 2 or a complement thereto. The polynucleotides maycomprise at least 21, 22, 23, 24, 25, 27, 30, 32, 35, 40, 45, 50, ormore consecutive bases of the nucleic acids sequence of a targetselected from Table 1 or Table 2, as applicable.

The polynucleotides may be provided in a variety of formats, includingas solids, in solution, or in an array. The polynucleotides mayoptionally comprise one or more labels, which may be chemically and/orenzymatically incorporated into the polynucleotide.

In some embodiments, one or more polynucleotides provided herein can beprovided on a substrate. The substrate can comprise a wide range ofmaterial, either biological, nonbiological, organic, inorganic, or acombination of any of these. For example, the substrate may be apolymerized Langmuir Blodgett film, functionalized glass, Si, Ge, GaAs,GaP, SiO₂, SiN₄, modified silicon, or any one of a wide variety of gelsor polymers such as (poly)tetrafluoroethylene,(poly)vinylidenedifluoride, polystyrene, cross-linked polystyrene,polyacrylic, polylactic acid, polyglycolic acid, poly(lactidecoglycolide), polyanhydrides, poly(methyl methacrylate),poly(ethylene-co-vinyl acetate), polysiloxanes, polymeric silica,latexes, dextran polymers, epoxies, polycarbonates, or combinationsthereof. Conducting polymers and photoconductive materials can be used.

The substrate can take the form of an array, a photodiode, anoptoelectronic sensor such as an optoelectronic semiconductor chip oroptoelectronic thin-film semiconductor, or a biochip. The location(s) ofprobe(s) on the substrate can be addressable; this can be done in highlydense formats, and the location(s) can be microaddressable ornanoaddressable.

Diagnostic Samples

A biological sample containing prostate cancer cells is collected from asubject in need of treatment for prostate cancer to evaluate whether apatient will benefit from radiation therapy. Diagnostic samples for usewith the systems and in the methods of the present invention comprisenucleic acids suitable for providing RNAs expression information. Inprinciple, the biological sample from which the expressed RNA isobtained and analyzed for target sequence expression can be any materialsuspected of comprising cancerous tissue or cells. The diagnostic samplecan be a biological sample used directly in a method of the invention.Alternatively, the diagnostic sample can be a sample prepared from abiological sample.

In one embodiment, the sample or portion of the sample comprising orsuspected of comprising cancerous tissue or cells can be any source ofbiological material, including cells, tissue or fluid, including bodilyfluids. Non-limiting examples of the source of the sample include anaspirate, a needle biopsy, a cytology pellet, a bulk tissue preparationor a section thereof obtained for example by surgery or autopsy, lymphfluid, blood, plasma, serum, tumors, and organs. In some embodiments,the sample is from urine. Alternatively, the sample is from blood,plasma or serum. In some embodiments, the sample is from saliva.

The samples may be archival samples, having a known and documentedmedical outcome, or may be samples from current patients whose ultimatemedical outcome is not yet known.

In some embodiments, the sample may be dissected prior to molecularanalysis. The sample may be prepared via macrodissection of a bulk tumorspecimen or portion thereof, or may be treated via microdissection, forexample via Laser Capture Microdissection (LCM).

The sample may initially be provided in a variety of states, as freshtissue, fresh frozen tissue, fine needle aspirates, and may be fixed orunfixed. Frequently, medical laboratories routinely prepare medicalsamples in a fixed state, which facilitates tissue storage. A variety offixatives can be used to fix tissue to stabilize the morphology ofcells, and may be used alone or in combination with other agents.Exemplary fixatives include crosslinking agents, alcohols, acetone,Bouin’s solution, Zenker solution, Hely solution, osmic acid solutionand Carnoy solution.

Crosslinking fixatives can comprise any agent suitable for forming twoor more covalent bonds, for example an aldehyde. Sources of aldehydestypically used for fixation include formaldehyde, paraformaldehyde,glutaraldehyde or formalin. Preferably, the crosslinking agent comprisesformaldehyde, which may be included in its native form or in the form ofparaformaldehyde or formalin. One of skill in the art would appreciatethat for samples in which crosslinking fixatives have been used specialpreparatory steps may be necessary including for example heating stepsand proteinase-k digestion; see methods.

One or more alcohols may be used to fix tissue, alone or in combinationwith other fixatives. Exemplary alcohols used for fixation includemethanol, ethanol and isopropanol.

Formalin fixation is frequently used in medical laboratories. Formalincomprises both an alcohol, typically methanol, and formaldehyde, both ofwhich can act to fix a biological sample.

Whether fixed or unfixed, the biological sample may optionally beembedded in an embedding medium. Exemplary embedding media used inhistology including paraffin, Tissue-Tek® V.I.P.TM, Paramat, ParamatExtra, Paraplast, Paraplast X-tra, Paraplast Plus, Peel Away ParaffinEmbedding Wax, Polyester Wax, Carbowax Polyethylene Glycol, PolyfinTM,Tissue Freezing Medium TFMFM, Cryo-GefTM, and OCT Compound (ElectronMicroscopy Sciences, Hatfield, PA). Prior to molecular analysis, theembedding material may be removed via any suitable techniques, as knownin the art. For example, where the sample is embedded in wax, theembedding material may be removed by extraction with organic solvent(s),for example xylenes. Kits are commercially available for removingembedding media from tissues. Samples or sections thereof may besubjected to further processing steps as needed, for example serialhydration or dehydration steps.

In some embodiments, the sample is a fixed, wax-embedded biologicalsample. Frequently, samples from medical laboratories are provided asfixed, wax-embedded samples, most commonly as formalin-fixed, paraffinembedded (FFPE) tissues.

Whatever the source of the biological sample, the target polynucleotidethat is ultimately assayed can be prepared synthetically (in the case ofcontrol sequences), but typically is purified from the biological sourceand subjected to one or more preparative steps. The RNA may be purifiedto remove or diminish one or more undesired components from thebiological sample or to concentrate it. Conversely, where the RNA is tooconcentrated for the particular assay, it may be diluted.

RNA Extraction

RNA can be extracted and purified from biological samples using anysuitable technique. A number of techniques are known in the art, andseveral are commercially available (e.g., FormaPure nucleic acidextraction kit, Agencourt Biosciences, Beverly MA, High Pure FFPE RNAMicro Kit, Roche Applied Science, Indianapolis, IN). RNA can beextracted from frozen tissue sections using TRIzol (Invitrogen,Carlsbad, CA) and purified using RNeasy Protect kit (Qiagen, Valencia,CA). RNA can be further purified using DNAse I treatment (Ambion,Austin, TX) to eliminate any contaminating DNA. RNA concentrations canbe made using a Nanodrop ND-1000 spectrophotometer (NanodropTechnologies, Rockland, DE). RNA can be further purified to eliminatecontaminants that interfere with cDNA synthesis by cold sodium acetateprecipitation. RNA integrity can be evaluated by runningelectropherograms, and RNA integrity number (RIN, a correlative measurethat indicates intactness of mRNA) can be determined using the RNA 6000PicoAssay for the Bioanalyzer 2100 (Agilent Technologies, Santa Clara,CA).

Kits

Kits for performing the desired method(s) are also provided, andcomprise a container or housing for holding the components of the kit,one or more vessels containing one or more nucleic acid(s), andoptionally one or more vessels containing one or more reagents. Thereagents include those described herein, and those reagents useful forperforming the methods described, including amplification reagents, andmay include one or more probes, primers or primer pairs, enzymes(including polymerases and ligases), intercalating dyes, labeled probes,and labels that can be incorporated into amplification products.

In some embodiments, the kit comprises primers or primer pairs specificfor those subsets and combinations of target sequences described herein.The primers or pairs of primers suitable for selectively amplifying thetarget sequences. The kit may comprise at least two, three, four or fiveprimers or pairs of primers suitable for selectively amplifying one ormore targets. The kit may comprise at least 5, 10, 15, 20, 30, 40, 50,60, 70, 80, 90, 100, 110, or more primers or pairs of primers suitablefor selectively amplifying one or more targets.

In some embodiments, the primers or primer pairs of the kit, when usedin an amplification reaction, specifically amplify a non-coding target,coding target, exonic, or non-exonic target described herein, a nucleicacid sequence corresponding to a target selected from Table 1 or Table2, an RNA form thereof, or a complement to either thereof. The kit mayinclude a plurality of such primers or primer pairs which canspecifically amplify a corresponding plurality of different amplify anon-coding target, coding target, exonic, or non-exonic transcriptdescribed herein, a nucleic acid sequence corresponding to a targetselected from Table 1 or Table 2, RNA forms thereof, or complementsthereto. At least two, three, four or five primers or pairs of primerssuitable for selectively amplifying the one or more targets can beprovided in kit form. In some embodiments, the kit comprises from fiveto fifty primers or pairs of primers suitable for amplifying the one ormore targets.

The reagents may independently be in liquid or solid form. The reagentsmay be provided in mixtures. Control samples and/or nucleic acids mayoptionally be provided in the kit. Control samples may include tissueand/or nucleic acids obtained from or representative of tumor samplesfrom patients showing no evidence of disease, as well as tissue and/ornucleic acids obtained from or representative of tumor samples frompatients that develop systemic cancer.

The nucleic acids may be provided in an array format, and thus an arrayor microarray may be included in the kit. The kit optionally may becertified by a government agency for use in prognosing the diseaseoutcome of cancer patients and/or for designating a treatment modality.

Instructions for using the kit to perform one or more methods of theinvention can be provided with the container, and can be provided in anyfixed medium. The instructions may be located inside or outside thecontainer or housing, and/or may be printed on the interior or exteriorof any surface thereof. A kit may be in multiplex form for concurrentlydetecting and/or quantitating one or more different targetpolynucleotides representing the expressed target sequences.

Amplification and Hybridization

Following sample collection and nucleic acid extraction, the nucleicacid portion of the sample comprising RNA that is or can be used toprepare the target polynucleotide(s) of interest can be subjected to oneor more preparative reactions. These preparative reactions can includein vitro transcription (IVT), labeling, fragmentation, amplification andother reactions. mRNA can first be treated with reverse transcriptaseand a primer to create cDNA prior to detection, quantitation and/oramplification; this can be done in vitro with purified mRNA or in situ,e.g., in cells or tissues affixed to a slide.

By “amplification” is meant any process of producing at least one copyof a nucleic acid, in this case an expressed RNA, and in many casesproduces multiple copies. An amplification product can be RNA or DNA,and may include a complementary strand to the expressed target sequence.DNA amplification products can be produced initially through reversetranslation and then optionally from further amplification reactions.The amplification product may include all or a portion of a targetsequence, and may optionally be labeled. A variety of amplificationmethods are suitable for use, including polymerase-based methods andligation-based methods. Exemplary amplification techniques include thepolymerase chain reaction method (PCR), the lipase chain reaction (LCR),ribozyme-based methods, self-sustained sequence replication (3SR),nucleic acid sequence-based amplification (NASBA), the use of Q Betareplicase, reverse transcription, nick translation, and the like.

Asymmetric amplification reactions may be used to preferentially amplifyone strand representing the target sequence that is used for detectionas the target polynucleotide. In some cases, the presence and/or amountof the amplification product itself may be used to determine theexpression level of a given target sequence. In other instances, theamplification product may be used to hybridize to an array or othersubstrate comprising sensor polynucleotides which are used to detectand/or quantitate target sequence expression.

The first cycle of amplification in polymerase-based methods typicallyforms a primer extension product complementary to the template strand.If the template is single-stranded RNA, a polymerase with reversetranscriptase activity is used in the first amplification to reversetranscribe the RNA to DNA, and additional amplification cycles can beperformed to copy the primer extension products. The primers for a PCRmust, of course, be designed to hybridize to regions in theircorresponding template that can produce an amplifiable segment; thus,each primer must hybridize so that its 3′ nucleotide is paired to anucleotide in its complementary template strand that is located 3′ fromthe 3′ nucleotide of the primer used to replicate that complementarytemplate strand in the PCR.

The target polynucleotide can be amplified by contacting one or morestrands of the target polynucleotide with a primer and a polymerasehaving suitable activity to extend the primer and copy the targetpolynucleotide to produce a full-length complementary polynucleotide ora smaller portion thereof. Any enzyme having a polymerase activity thatcan copy the target polynucleotide can be used, including DNApolymerases, RNA polymerases, reverse transcriptases, and enzymes havingmore than one type of polymerase or enzyme activity. The enzyme can bethermolabile or thermostable. Mixtures of enzymes can also be used.Exemplary enzymes include: DNA polymerases such as DNA Polymerase I(“Pol I”), the Klenow fragment of Pol I, T4, T7, Sequenase® T7,Sequenase® Version 2.0 T7, Tub, Taq, Tth, Pfic, Pfu, Tsp, Tfl, Tli andPyrococcus sp GB-D DNA polymerases; RNA polymerases such as E. coil,SP6, T3 and T7 RNA polymerases; and reverse transcriptases such as AMV,M-MuLV, MMLV, RNAse H MMLV (SuperScript®), SuperScript® II,ThermoScript®, HIV-1, and RAV2 reverse transcriptases. All of theseenzymes are commercially available. Exemplary polymerases with multiplespecificities include RAV2 and Tli (exo-) polymerases. Exemplarythermostable polymerases include Tub, Taq, Tth, Pfic, Pfu, Tsp, Tfl, Tliand Pyrococcus sp. GB-D DNA polymerases.

Suitable reaction conditions are chosen to permit amplification of thetarget polynucleotide, including pH, buffer, ionic strength, presenceand concentration of one or more salts, presence and concentration ofreactants and cofactors such as nucleotides and magnesium and/or othermetal ions (e.g., manganese), optional cosolvents, temperature, thermalcycling profile for amplification schemes comprising a polymerase chainreaction, and may depend in part on the polymerase being used as well asthe nature of the sample. Cosolvents include formamide (typically atfrom about 2 to about 10 %), glycerol (typically at from about 5 toabout 10 %), and DMSO (typically at from about 0.9 to about 10 %).Techniques may be used in the amplification scheme in order to minimizethe production of false positives or artifacts produced duringamplification. These include “touchdown” PCR, hot-start techniques, useof nested primers, or designing PCR primers so that they form stem-loopstructures in the event of primer-dimer formation and thus are notamplified. Techniques to accelerate PCR can be used, for examplecentrifugal PCR, which allows for greater convection within the sample,and comprising infrared heating steps for rapid heating and cooling ofthe sample. One or more cycles of amplification can be performed. Anexcess of one primer can be used to produce an excess of one primerextension product during PCR; preferably, the primer extension productproduced in excess is the amplification product to be detected. Aplurality of different primers may be used to amplify different targetpolynucleotides or different regions of a particular targetpolynucleotide within the sample.

An amplification reaction can be performed under conditions which allowan optionally labeled sensor polynucleotide to hybridize to theamplification product during at least part of an amplification cycle.When the assay is performed in this manner, real-time detection of thishybridization event can take place by monitoring for light emission orfluorescence during amplification, as known in the art.

Where the amplification product is to be used for hybridization to anarray or microarray, a number of suitable commercially availableamplification products are available. These include amplification kitsavailable from NuGEN, Inc. (San Carlos, CA), including the WT-OvationTmSystem, WT-OvationTm System v2, WT-OvationTm Pico System, WT-OvationTmFFPE Exon Module, WT-OvationTm FFPE Exon Module RiboAmp and RiboAmp^(Plus) RNA Amplification Kits (MDS Analytical Technologies (formerlyArcturus) (Mountain View, CA), Genisphere, Inc. (Hatfield, PA),including the RampUp PlusTM and SenseAmpTM RNA Amplification kits, aloneor in combination. Amplified nucleic acids may be subjected to one ormore purification reactions after amplification and labeling, forexample using magnetic beads (e.g., RNAClean magnetic beads, AgencourtBiosciences).

Multiple RNA biomarkers can be analyzed using real-time quantitativemultiplex RT-PCR platforms and other multiplexing technologies such asGenomeLab GeXP Genetic Analysis System (Beckman Coulter, Foster City,CA), SmartCycler® 9600 or GeneXpert® Systems (Cepheid, Sunnyvale, CA),ABI 7900 HT Fast Real Time PCR system (Applied Biosystems, Foster City,CA), LightCycler® 480 System (Roche Molecular Systems, Pleasanton, CA),xMAP 100 System (Luminex, Austin, TX) Solexa Genome Analysis System(Illumina, Hayward, CA), OpenArray Real Time qPCR (BioTrove, Woburn, MA)and BeadXpress System (Illumina, Hayward, CA).

Detection and/or Quantification of Target Sequences

Any method of detecting and/or quantitating the expression of theencoded target sequences can in principle be used in the invention. Theexpressed target sequences can be directly detected and/or quantitated,or may be copied and/or amplified to allow detection of amplified copiesof the expressed target sequences or its complement.

Methods for detecting and/or quantifying a target can include Northernblotting, sequencing, array or microarray hybridization, serial analysisof gene expression (SAGE), by enzymatic cleavage of specific structures(e.g., an Invader® assay, Third Wave Technologies, e.g. as described inU.S. Pat. Nos. 5,846,717, 6,090,543; 6,001,567; 5,985,557; and5,994,069) and amplification methods, e.g. RT-PCR, including in aTaqMan® assay (PE Biosystems, Foster City, Calif., e.g. as described inU.S. Pat. Nos. 5,962,233 and 5,538,848), and may be quantitative orsemi-quantitative, and may vary depending on the origin, amount andcondition of the available biological sample. Combinations of thesemethods may also be used. For example, nucleic acids may be amplified,labeled and subjected to microarray analysis.

In some instances, target sequences may be detected by sequencing.Sequencing methods may comprise whole genome sequencing or exomesequencing. Sequencing methods such as Maxim-Gilbert, chain-termination,or high-throughput systems may also be used. Additional, suitablesequencing techniques include classic dideoxy sequencing reactions(Sanger method) using labeled terminators or primers and gel separationin slab or capillary, sequencing by synthesis using reversiblyterminated labeled nucleotides, pyrosequencing, 454 sequencing, allelespecific hybridization to a library of labeled oligonucleotide probes,sequencing by synthesis using allele specific hybridization to a libraryof labeled clones that is followed by ligation, real time monitoring ofthe incorporation of labeled nucleotides during a polymerization step,and SOLiD sequencing.

Additional methods for detecting and/or quantifying a target includesingle-molecule sequencing (e.g., Helicos, PacBio), sequencing bysynthesis (e.g., Illumina, Ion Torrent), sequencing by ligation (e.g.,ABI SOLID), sequencing by hybridization (e.g., Complete Genomics), insitu hybridization, bead-array technologies (e.g., Luminex xMAP,Illumina BeadChips), branched DNA technology (e.g., Panomics,Genisphere). Sequencing methods may use fluorescent (e.g., Illumina) orelectronic (e.g., Ion Torrent, Oxford Nanopore) methods of detectingnucleotides.

Reverse Transcription for QRT-PCR Analysis

Reverse transcription can be performed by any method known in the art.For example, reverse transcription may be performed using the Omniscriptkit (Qiagen, Valencia, CA), Superscript III kit (Invitrogen, Carlsbad,CA), for RT-PCR. Target-specific priming can be performed in order toincrease the sensitivity of detection of target sequences and generatetarget-specific cDNA.

TaqMan® Gene Expression Analysis

TaqMan®RT-PCR can be performed using Applied Biosystems Prism (ABI) 7900HT instruments in a 51.11 volume with target sequence-specific cDNAequivalent to 1 ng total RNA.

Primers and probes concentrations for TaqMan analysis are added toamplify fluorescent amplicons using PCR cycling conditions such as 95°C. for 10 minutes for one cycle, 95° C. for 20 seconds, and 60° C. for45 seconds for 40 cycles. A reference sample can be assayed to ensurereagent and process stability. Negative controls (e.g., no template)should be assayed to monitor any exogenous nucleic acid contamination.

Classification Arrays

The present invention contemplates that a probe set or probes derivedtherefrom may be provided in an array format. In the context of thepresent invention, an “array” is a spatially or logically organizedcollection of polynucleotide probes. An array comprising probes specificfor a coding target, non-coding target, or a combination thereof may beused. Alternatively, an array comprising probes specific for two or moreof the transcripts of a target selected from Table 2, or a productderived thereof, can be used. Desirably, an array may be specific for 5,10, 15, 20, 25, 30 or more of the transcripts of a target selected fromTable 2. Probes useful for the methods of the present invention areprovided in Table 1. Expression of these sequences may be detected aloneor in combination with other transcripts. In some embodiments, an arrayis used which comprises a wide range of sensor probes forprostate-specific expression products, along with appropriate controlsequences. In some instances, the array may comprise the Human Exon 1.0ST Array (HuEx 1.0 ST, Affymetrix, Inc., Santa Clara, CA.).

Typically the polynucleotide probes are attached to a solid substrateand are ordered so that the location (on the substrate) and the identityof each are known. The polynucleotide probes can be attached to one of avariety of solid substrates capable of withstanding the reagents andconditions necessary for use of the array. Examples include, but are notlimited to, polymers, such as (poly)tetrafluoroethylene,(poly)vinylidenedifluoride, polystyrene, polycarbonate, polypropyleneand polystyrene; ceramic; silicon; silicon dioxide; modified silicon;(fused) silica, quartz or glass; functionalized glass; paper, such asfilter paper; diazotized cellulose; nitrocellulose filter; nylonmembrane; and polyacrylamide gel pad. Substrates that are transparent tolight are useful for arrays that may be used in an assay that involvesoptical detection.

Examples of array formats include membrane or filter arrays (forexample, nitrocellulose, nylon arrays), plate arrays (for example,multiwell, such as a 24-, 96-, 256-, 384-, 864- or 1536-well, microtitreplate arrays), pin arrays, and bead arrays (for example, in a liquid“slurry”). Arrays on substrates such as glass or ceramic slides areoften referred to as chip arrays or “chips.” Such arrays are well knownin the art. In one embodiment of the present invention, the CancerPrognosticarray is a chip.

Data Analysis

In some embodiments, one or more pattern recognition methods can be usedin analyzing the expression level of target sequences. The patternrecognition method can comprise a linear combination of expressionlevels, or a nonlinear combination of expression levels. In someembodiments, expression measurements for RNA transcripts or combinationsof RNA transcript levels are formulated into linear or non-linear modelsor algorithms (e.g., an ‘expression signature’) and converted into alikelihood score. This likelihood score may indicate the probabilitythat a biological sample is from a patient who will benefit fromradiation therapy. Additionally, a likelihood score may indicate theprobability that a biological sample is from a patient who may exhibitno evidence of disease, who may exhibit systemic cancer, or who mayexhibit biochemical recurrence. The likelihood score can be used todistinguish these disease states. The models and/or algorithms can beprovided in machine readable format, and may be used to correlateexpression levels or an expression profile with a disease state, and/orto designate a treatment modality for a patient or class of patients.

Assaying the expression level for a plurality of targets may comprisethe use of an algorithm or classifier. Array data can be managed,classified, and analyzed using techniques known in the art. Assaying theexpression level for a plurality of targets may comprise probe setmodeling and data pre-processing. Probe set modeling and datapre-processing can be derived using the Robust Multi-Array (RMA)algorithm or variants GC-RMA, fRMA, Probe Logarithmic Intensity Error(PLIER) algorithm, or variant iterPLIER, or Single-Channel ArrayNormalization (SCAN) algorithm. Variance or intensity filters can beapplied to pre-process data using the RMA algorithm, for example byremoving target sequences with a standard deviation of < 10 or a meanintensity of < 100 intensity units of a normalized data range,respectively.

Alternatively, assaying the expression level for a plurality of targetsmay comprise the use of a machine learning algorithm. The machinelearning algorithm may comprise a supervised learning algorithm.Examples of supervised learning algorithms may include AverageOne-Dependence Estimators (AODE), Artificial neural network (e.g.,Backpropagation), Bayesian statistics (e.g., Naive Bayes classifier,Bayesian network, Bayesian knowledge base), Case-based reasoning,Decision trees, Inductive logic programming, Gaussian processregression, Group method of data handling (GMDH), Learning Automata,Learning Vector Quantization, Minimum message length (decision trees,decision graphs, etc.), Lazy learning, Instance-based learning NearestNeighbor Algorithm, Analogical modeling, Probably approximately correctlearning (PAC) learning, Ripple down rules, a knowledge acquisitionmethodology, Symbolic machine learning algorithms, Subsymbolic machinelearning algorithms, Support vector machines, Random Forests, Ensemblesof classifiers, Bootstrap aggregating (bagging), and Boosting.Supervised learning may comprise ordinal classification such asregression analysis and Information fuzzy networks (IFN). Alternatively,supervised learning methods may comprise statistical classification,such as AODE, Linear classifiers (e.g., Fisher’s linear discriminant,Logistic regression, Naive Bayes classifier, Perceptron, and Supportvector machine), quadratic classifiers, k-nearest neighbor, Boosting,Decision trees (e.g., C4.5, Random forests), Bayesian networks, andHidden Markov models.

The machine learning algorithms may also comprise an unsupervisedlearning algorithm. Examples of unsupervised learning algorithms mayinclude artificial neural network, Data clustering,Expectation-maximization algorithm, Self-organizing map, Radial basisfunction network, Vector Quantization, Generative topographic map,Information bottleneck method, and IBSEAD. Unsupervised learning mayalso comprise association rule learning algorithms such as Apriorialgorithm, Eclat algorithm and FP-growth algorithm. Hierarchicalclustering, such as Single-linkage clustering and Conceptual clustering,may also be used. Alternatively, unsupervised learning may comprisepartitional clustering such as K-means algorithm and Fuzzy clustering.

In some instances, the machine learning algorithms comprise areinforcement learning algorithm. Examples of reinforcement learningalgorithms include, but are not limited to, temporal differencelearning, Q-learning and Learning Automata. Alternatively, the machinelearning algorithm may comprise Data Pre-processing.

Preferably, the machine learning algorithms may include, but are notlimited to, Average One-Dependence Estimators (AODE), Fisher’s lineardiscriminant, Logistic regression, Perceptron, Multilayer Perceptron,Artificial Neural Networks, Support vector machines, Quadraticclassifiers, Boosting, Decision trees, C4.5, Bayesian networks, HiddenMarkov models, High-Dimensional Discriminant Analysis, and GaussianMixture Models. The machine learning algorithm may comprise supportvector machines, Naive Bayes classifier, k-nearest neighbor,high-dimensional discriminant analysis, or Gaussian mixture models. Insome instances, the machine learning algorithm comprises Random Forests.

Therapeutic Regimens

Diagnosing, predicting, or monitoring a status or outcome of prostatecancer may comprise treating prostate cancer or preventing cancerprogression. In addition, diagnosing, predicting, or monitoring a statusor outcome of prostate cancer may comprise identifying or predictingwhich patients will be responders or non-responders to an anti-cancertherapy (e.g., radiation therapy). In some instances, diagnosing,predicting, or monitoring may comprise determining a therapeuticregimen. Determining a therapeutic regimen may comprise administering ananti-cancer therapy. Alternatively, determining a therapeutic regimenmay comprise modifying, recommending, continuing or discontinuing ananti-cancer regimen. In some instances, if the sample expressionpatterns are consistent with the expression pattern for a known diseaseor disease outcome, the expression patterns can be used to designate oneor more treatment modalities (e.g., therapeutic regimens, such asradiation therapy or other anti-cancer regimen). An anti-cancer regimenmay comprise one or more anti-cancer therapies. Examples of anti-cancertherapies include surgery, chemotherapy, radiation therapy,immunotherapy/biological therapy, and photodynamic therapy.

For example, a patient is selected for treatment with radiation therapyif the patient is identified as likely to be responsive to radiationtherapy based on an expression profile or PORTOS, as described herein.The radiation used in treatment can come from a machine outside the body(external-beam radiation therapy) or from radioactive material placed inthe body near cancer cells (internal radiation therapy, more commonlycalled brachytherapy). Systemic radiation therapy uses a radioactivesubstance, given by mouth or into a vein that travels in the blood totissues throughout the body.

External-beam radiation therapy may be delivered in the form of photonbeams (either x-rays or gamma rays). A photon is the basic unit of lightand other forms of electromagnetic radiation. An example ofexternal-beam radiation therapy is called 3-dimensional conformalradiation therapy (3D-CRT). 3D-CRT may use computer software andadvanced treatment machines to deliver radiation to very preciselyshaped target areas. Many other methods of external-beam radiationtherapy are currently being tested and used in cancer treatment. Thesemethods include, but are not limited to, intensity-modulated radiationtherapy (IMRT), image-guided radiation therapy (IGRT), Stereotacticradiosurgery (SRS), Stereotactic body radiation therapy (SBRT), andproton therapy.

Intensity-modulated radiation therapy (IMRT) is an example ofexternal-beam radiation and may use hundreds of tiny radiationbeam-shaping devices, called collimators, to deliver a single dose ofradiation. The collimators can be stationary or can move duringtreatment, allowing the intensity of the radiation beams to changeduring treatment sessions. This kind of dose modulation allows differentareas of a tumor or nearby tissues to receive different doses ofradiation. IMRT is planned in reverse (called inverse treatmentplanning). In inverse treatment planning, the radiation doses todifferent areas of the tumor and surrounding tissue are planned inadvance, and then a high-powered computer program calculates therequired number of beams and angles of the radiation treatment. Incontrast, during traditional (forward) treatment planning, the numberand angles of the radiation beams are chosen in advance and computerscalculate how much dose may be delivered from each of the planned beams.The goal of IMRT is to increase the radiation dose to the areas thatneed it and reduce radiation exposure to specific sensitive areas ofsurrounding normal tissue.

Another example of external-beam radiation is image-guided radiationtherapy (IGRT). In IGRT, repeated imaging scans (CT, MRI, or PET) may beperformed during treatment. These imaging scans may be processed bycomputers to identify changes in a tumor’s size and location due totreatment and to allow the position of the patient or the plannedradiation dose to be adjusted during treatment as needed. Repeatedimaging can increase the accuracy of radiation treatment and may allowreductions in the planned volume of tissue to be treated, therebydecreasing the total radiation dose to normal tissue.

Tomotherapy is a type of image-guided IMRT. A tomotherapy machine is ahybrid between a CT imaging scanner and an external-beam radiationtherapy machine. The part of the tomotherapy machine that deliversradiation for both imaging and treatment can rotate completely aroundthe patient in the same manner as a normal CT scanner. Tomotherapymachines can capture CT images of the patient’s tumor immediately beforetreatment sessions, to allow for very precise tumor targeting andsparing of normal tissue.

Stereotactic radiosurgery (SRS) can deliver one or more high doses ofradiation to a small tumor. SRS uses extremely accurate image-guidedtumor targeting and patient positioning. Therefore, a high dose ofradiation can be given without excess damage to normal tissue. SRS canbe used to treat small tumors with well-defined edges. It is mostcommonly used in the treatment of brain or spinal tumors and brainmetastases from other cancer types. For the treatment of some brainmetastases, patients may receive radiation therapy to the entire brain(called whole-brain radiation therapy) in addition to SRS. SRS requiresthe use of a head frame or other device to immobilize the patient duringtreatment to ensure that the high dose of radiation is deliveredaccurately.

Stereotactic body radiation therapy (SBRT) delivers radiation therapy infewer sessions, using smaller radiation fields and higher doses than3D-CRT in most cases. SBRT may treat tumors that lie outside the brainand spinal cord. Because these tumors are more likely to move with thenormal motion of the body, and therefore cannot be targeted asaccurately as tumors within the brain or spine, SBRT is usually given inmore than one dose. SBRT can be used to treat small, isolated tumors,including cancers in the lung and liver. SBRT systems may be known bytheir brand names, such as the CyberKnife®.

In proton therapy, external-beam radiation therapy may be delivered byproton. Protons are a type of charged particle. Proton beams differ fromphoton beams mainly in the way they deposit energy in living tissue.Whereas photons deposit energy in small packets all along their paththrough tissue, protons deposit much of their energy at the end of theirpath (called the Bragg peak) and deposit less energy along the way. Useof protons may reduce the exposure of normal tissue to radiation,possibly allowing the delivery of higher doses of radiation to a tumor.

Other charged particle beams such as electron beams may be used toirradiate superficial tumors, such as skin cancer or tumors near thesurface of the body, but they cannot travel very far through tissue.

Internal radiation therapy (brachytherapy) is radiation delivered fromradiation sources (radioactive materials) placed inside or on the body.Several brachytherapy techniques are used in cancer treatment.Interstitial brachytherapy may use a radiation source placed withintumor tissue, such as within a prostate tumor. Intracavitarybrachytherapy may use a source placed within a surgical cavity or a bodycavity, such as the chest cavity, near a tumor. Episcleralbrachytherapy, which may be used to treat melanoma inside the eye, mayuse a source that is attached to the eye. In brachytherapy, radioactiveisotopes can be sealed in tiny pellets or “seeds.” These seeds may beplaced in patients using delivery devices, such as needles, catheters,or some other type of carrier. As the isotopes decay naturally, theygive off radiation that may damage nearby cancer cells. Brachytherapymay be able to deliver higher doses of radiation to some cancers thanexternal-beam radiation therapy while causing less damage to normaltissue.

Brachytherapy can be given as a low-dose-rate or a high-dose-ratetreatment. In low-dose-rate treatment, cancer cells receive continuouslow-dose radiation from the source over a period of several days. Inhigh-dose-rate treatment, a robotic machine attached to delivery tubesplaced inside the body may guide one or more radioactive sources into ornear a tumor, and then removes the sources at the end of each treatmentsession. High-dose-rate treatment can be given in one or more treatmentsessions. An example of a high-dose-rate treatment is the MammoSite®system. Bracytherapy may be used to treat patients with breast cancerwho have undergone breast-conserving surgery.

The placement of brachytherapy sources can be temporary or permanent.For permanent brachytherapy, the sources may be surgically sealed withinthe body and left there, even after all of the radiation has been givenoff. In some instances, the remaining material (in which the radioactiveisotopes were sealed) does not cause any discomfort or harm to thepatient. Permanent brachytherapy is a type of low-dose-ratebrachytherapy. For temporary brachytherapy, tubes (catheters) or othercarriers are used to deliver the radiation sources, and both thecarriers and the radiation sources are removed after treatment.Temporary brachytherapy can be either low-dose-rate or high-dose-ratetreatment. Brachytherapy may be used alone or in addition toexternal-beam radiation therapy to provide a “boost” of radiation to atumor while sparing surrounding normal tissue.

In systemic radiation therapy, a patient may swallow or receive aninjection of a radioactive substance, such as radioactive iodine or aradioactive substance bound to a monoclonal antibody. Radioactive iodine(131I) is a type of systemic radiation therapy commonly used to helptreat cancer, such as thyroid cancer. Thyroid cells naturally take upradioactive iodine. For systemic radiation therapy for some other typesof cancer, a monoclonal antibody may help target the radioactivesubstance to the right place. The antibody joined to the radioactivesubstance travels through the blood, locating and killing tumor cells.For example, the drug ibritumomab tiuxetan (Zevalin®) may be used forthe treatment of certain types of B-cell non-Hodgkin lymphoma (NHL). Theantibody part of this drug recognizes and binds to a protein found onthe surface of B lymphocytes. The combination drug regimen oftositumomab and iodine I 131 tositumomab (Bexxar®) may be used for thetreatment of certain types of cancer, such as NHL. In this regimen,nonradioactive tositumomab antibodies may be given to patients first,followed by treatment with tositumomab antibodies that have 131Iattached. Tositumomab may recognize and bind to the same protein on Blymphocytes as ibritumomab. The nonradioactive form of the antibody mayhelp protect normal B lymphocytes from being damaged by radiation from131I.

Some systemic radiation therapy drugs relieve pain from cancer that hasspread to the bone (bone metastases). This is a type of palliativeradiation therapy. The radioactive drugs samarium-153-lexidronam(Quadramet®) and strontium-89 chloride (Metastron®) are examples ofradiopharmaceuticals may be used to treat pain from bone metastases.

In addition, patients, especially those not identified as likely tobenefit from radiation therapy, may be administered other cancertreatments such as, but not limited to, surgery, chemotherapy,immunotherapy, hormonal therapy, biologic therapy, or any combinationthereof.

Surgical oncology uses surgical methods to diagnose, stage, and treatcancer, and to relieve certain cancer-related symptoms. Surgery may beused to remove the tumor (e.g., excisions, resections, debulkingsurgery), reconstruct a part of the body (e.g., restorative surgery),and/or to relieve symptoms such as pain (e.g., palliative surgery).Surgery may also include cryosurgery. Cryosurgery (also calledcryotherapy) may use extreme cold produced by liquid nitrogen (or argongas) to destroy abnormal tissue. Cryosurgery can be used to treatexternal tumors, such as those on the skin. For external tumors, liquidnitrogen can be applied directly to the cancer cells with a cotton swabor spraying device. Cryosurgery may also be used to treat tumors insidethe body (internal tumors and tumors in the bone). For internal tumors,liquid nitrogen or argon gas may be circulated through a hollowinstrument called a cryoprobe, which is placed in contact with thetumor. An ultrasound or MRI may be used to guide the cryoprobe andmonitor the freezing of the cells, thus limiting damage to nearbyhealthy tissue. A ball of ice crystals may form around the probe,freezing nearby cells. Sometimes more than one probe is used to deliverthe liquid nitrogen to various parts of the tumor. The probes may be putinto the tumor during surgery or through the skin (percutaneously).After cryosurgery, the frozen tissue thaws and may be naturally absorbedby the body (for internal tumors), or may dissolve and form a scab (forexternal tumors).

Chemotherapeutic agents may also be used for the treatment of prostatecancer. Examples of chemotherapeutic agents include alkylating agents,anti-metabolites, plant alkaloids and terpenoids, vinca alkaloids,podophyllotoxin, taxanes, topoisomerase inhibitors, and cytotoxicantibiotics. Cisplatin, carboplatin, and oxaliplatin are examples ofalkylating agents. Other alkylating agents include mechlorethamine,cyclophosphamide, chlorambucil, ifosfamide. Alkylating agents may impaircell function by forming covalent bonds with the amino, carboxyl,sulfhydryl, and phosphate groups in biologically important molecules.Alternatively, alkylating agents may chemically modify a cell’s DNA.

Anti-metabolites are another example of chemotherapeutic agents.Anti-metabolites may masquerade as purines or pyrimidines and mayprevent purines and pyrimidines from becoming incorporated in to DNAduring the “S” phase (of the cell cycle), thereby stopping normaldevelopment and division. Antimetabolites may also affect RNA synthesis.Examples of metabolites include azathioprine and mercaptopurine.

Alkaloids may be derived from plants and block cell division may also beused for the treatment of cancer. Alkyloids may prevent microtubulefunction. Examples of alkaloids are vinca alkaloids and taxanes. Vincaalkaloids may bind to specific sites on tubulin and inhibit the assemblyof tubulin into microtubules (M phase of the cell cycle). The vincaalkaloids may be derived from the Madagascar periwinkle, Catharanthusroseus (formerly known as Vinca rosea). Examples of vinca alkaloidsinclude, but are not limited to, vincristine, vinblastine, vinorelbine,or vindesine. Taxanes are diterpenes produced by the plants of the genusTaxus (yews). Taxanes may be derived from natural sources or synthesizedartificially. Taxanes include paclitaxel (Taxol) and docetaxel(Taxotere). Taxanes may disrupt microtubule function. Microtubules areessential to cell division, and taxanes may stabilize GDP-bound tubulinin the microtubule, thereby inhibiting the process of cell division.Thus, in essence, taxanes may be mitotic inhibitors. Taxanes may also beradiosensitizing and often contain numerous chiral centers.

Alternative chemotherapeutic agents include podophyllotoxin.Podophyllotoxin is a plant-derived compound that may help with digestionand may be used to produce cytostatic drugs such as etoposide andteniposide. They may prevent the cell from entering the G1 phase (thestart of DNA replication) and the replication of DNA (the S phase).

Topoisomerases are essential enzymes that maintain the topology of DNA.Inhibition of type I or type II topoisomerases may interfere with bothtranscription and replication of DNA by upsetting proper DNAsupercoiling. Some chemotherapeutic agents may inhibit topoisomerases.For example, some type I topoisomerase inhibitors include camptothecins:irinotecan and topotecan. Examples of type II inhibitors includeamsacrine, etoposide, etoposide phosphate, and teniposide.

Another example of chemotherapeutic agents is cytotoxic antibiotics.Cytotoxic antibiotics are a group of antibiotics that are used for thetreatment of cancer because they may interfere with DNA replicationand/or protein synthesis. Cytotoxic antiobiotics include, but are notlimited to, actinomycin, anthracyclines, doxorubicin, daunorubicin,valrubicin, idarubicin, epirubicin, bleomycin, plicamycin, andmitomycin.

Alternatively or additionally, the anti-cancer treatment may compriseimmunotherapy (sometimes called, biological therapy, biotherapy,biologic therapy, or biological response modifier (BRM) therapy), whichuses the body’s immune system, either directly or indirectly, to fightcancer or to lessen the side effects that may be caused by some cancertreatments. Immunotherapies include interferons, interleukins,colony-stimulating factors, monoclonal antibodies, vaccines, immunecell-based therapy, gene therapy, and nonspecific immunomodulatingagents.

Interferons (IFNs) are types of cytokines that occur naturally in thebody. Interferon alpha, interferon beta, and interferon gamma areexamples of interferons that may be used in cancer treatment.

Like interferons, interleukins (ILs) are cytokines that occur naturallyin the body and can be made in the laboratory. Many interleukins havebeen identified for the treatment of cancer. For example, interleukin-2(IL-2 or aldesleukin), interleukin 7, and interleukin 12 have may beused as an anti-cancer treatment. IL-2 may stimulate the growth andactivity of many immune cells, such as lymphocytes, that can destroycancer cells. Interleukins may be used to treat a number of cancers,including leukemia, lymphoma, and brain, colorectal, ovarian, breast,kidney and prostate cancers.

Colony-stimulating factors (CSFs) (sometimes called hematopoietic growthfactors) may also be used for the treatment of cancer. Some examples ofCSFs include, but are not limited to, G-CSF (filgrastim) and GM-CSF(sargramostim). CSFs may promote the division of bone marrow stem cellsand their development into white blood cells, platelets, and red bloodcells. Bone marrow is critical to the body’s immune system because it isthe source of all blood cells. Because anticancer drugs can damage thebody’s ability to make white blood cells, red blood cells, andplatelets, stimulation of the immune system by CSFs may benefit patientsundergoing other anti-cancer treatment, thus CSFs may be combined withother anti-cancer therapies, such as chemotherapy. CSFs may be used totreat a large variety of cancers, including lymphoma, leukemia, multiplemyeloma, melanoma, and cancers of the brain, lung, esophagus, breast,uterus, ovary, prostate, kidney, colon, and rectum.

Another type of immunotherapy includes monoclonal antibodies (MOABs orMoABs). These antibodies may be produced by a single type of cell andmay be specific for a particular antigen. To create MOABs, a humancancer cells may be injected into mice. In response, the mouse immunesystem can make antibodies against these cancer cells. The mouse plasmacells that produce antibodies may be isolated and fused withlaboratory-grown cells to create “hybrid” cells called hybridomas.Hybridomas can indefinitely produce large quantities of these pureantibodies, or MOABs. MOABs may be used in cancer treatment in a numberof ways. For instance, MOABs that react with specific types of cancermay enhance a patient’s immune response to the cancer. MOABs can beprogrammed to act against cell growth factors, thus interfering with thegrowth of cancer cells.

MOABs may be linked to other anti-cancer therapies such aschemotherapeutics, radioisotopes (radioactive substances), otherbiological therapies, or other toxins. When the antibodies latch ontocancer cells, they deliver these anti-cancer therapies directly to thetumor, helping to destroy it. MOABs carrying radioisotopes may alsoprove useful in diagnosing certain cancers, such as colorectal, ovarian,and prostate.

Rituxan® (rituximab) and Herceptin® (trastuzumab) are examples of MOABsthat may be used as a biological therapy. Rituxan may be used for thetreatment of non-Hodgkin lymphoma. Herceptin can be used to treatmetastatic breast cancer in patients with tumors that produce excessamounts of a protein called HER2. Alternatively, MOABs may be used totreat lymphoma, leukemia, melanoma, and cancers of the brain, breast,lung, kidney, colon, rectum, ovary, prostate, and other areas.

Cancer vaccines are another form of immunotherapy. Cancer vaccines maybe designed to encourage the patient’s immune system to recognize cancercells. Cancer vaccines may be designed to treat existing cancers(therapeutic vaccines) or to prevent the development of cancer(prophylactic vaccines). Therapeutic vaccines may be injected in aperson after cancer is diagnosed. These vaccines may stop the growth ofexisting tumors, prevent cancer from recurring, or eliminate cancercells not killed by prior treatments. Cancer vaccines given when thetumor is small may be able to eradicate the cancer. On the other hand,prophylactic vaccines are given to healthy individuals before cancerdevelops. These vaccines are designed to stimulate the immune system toattack viruses that can cause cancer. By targeting these cancer-causingviruses, development of certain cancers may be prevented. For example,cervarix and gardasil are vaccines to treat human papilloma virus andmay prevent cervical cancer. Therapeutic vaccines may be used to treatmelanoma, lymphoma, leukemia, and cancers of the brain, breast, lung,kidney, ovary, prostate, pancreas, colon, and rectum. Cancer vaccinescan be used in combination with other anti-cancer therapies.

Immune cell-based therapy is also another form of immunotherapy.Adoptive cell transfer may include the transfer of immune cells such asdendritic cells, T cells (e.g., cytotoxic T cells), or natural killer(NK) cells to activate a cytotoxic response or attack cancer cells in apatient. Autologous immune cell-based therapy involves the transfer of apatient’s own immune cells after expansion in vitro.

Gene therapy is another example of a biological therapy. Gene therapymay involve introducing genetic material into a person’s cells to fightdisease. Gene therapy methods may improve a patient’s immune response tocancer. For example, a gene may be inserted into an immune cell toenhance its ability to recognize and attack cancer cells. In anotherapproach, cancer cells may be injected with genes that cause the cancercells to produce cytokines and stimulate the immune system.

In some instances, biological therapy includes nonspecificimmunomodulating agents. Nonspecific immunomodulating agents aresubstances that stimulate or indirectly augment the immune system.Often, these agents target key immune system cells and may causesecondary responses such as increased production of cytokines andimmunoglobulins. Two nonspecific immunomodulating agents used in cancertreatment are bacillus Calmette-Guerin (BCG) and levamisole. BCG may beused in the treatment of superficial bladder cancer following surgery.BCG may work by stimulating an inflammatory, and possibly an immune,response. A solution of BCG may be instilled in the bladder. Levamisoleis sometimes used along with fluorouracil (5-FU) chemotherapy in thetreatment of stage III (Dukes′ C) colon cancer following surgery.Levamisole may act to restore depressed immune function.

Photodynamic therapy (PDT) is an anti-cancer treatment that may use adrug, called a photosensitizer or photosensitizing agent, and aparticular type of light. When photosensitizers are exposed to aspecific wavelength of light, they may produce a form of oxygen thatkills nearby cells. A photosensitizer may be activated by light of aspecific wavelength. This wavelength determines how far the light cantravel into the body. Thus, photosensitizers and wavelengths of lightmay be used to treat different areas of the body with PDT.

In the first step of PDT for cancer treatment, a photosensitizing agentmay be injected into the bloodstream. The agent may be absorbed by cellsall over the body but may stay in cancer cells longer than it does innormal cells. Approximately 24 to 72 hours after injection, when most ofthe agent has left normal cells but remains in cancer cells, the tumorcan be exposed to light. The photosensitizer in the tumor can absorb thelight and produces an active form of oxygen that destroys nearby cancercells. In addition to directly killing cancer cells, PDT may shrink ordestroy tumors in two other ways. The photosensitizer can damage bloodvessels in the tumor, thereby preventing the cancer from receivingnecessary nutrients. PDT may also activate the immune system to attackthe tumor cells.

The light used for PDT can come from a laser or other sources. Laserlight can be directed through fiber optic cables (thin fibers thattransmit light) to deliver light to areas inside the body. For example,a fiber optic cable can be inserted through an endoscope (a thin,lighted tube used to look at tissues inside the body) into the lungs oresophagus to treat cancer in these organs. Other light sources includelight-emitting diodes (LEDs), which may be used for surface tumors, suchas skin cancer. PDT is usually performed as an outpatient procedure. PDTmay also be repeated and may be used with other therapies, such assurgery, radiation, or chemotherapy.

Extracorporeal photopheresis (ECP) is a type of PDT in which a machinemay be used to collect the patient’s blood cells. The patient’s bloodcells may be treated outside the body with a photosensitizing agent,exposed to light, and then returned to the patient. ECP may be used tohelp lessen the severity of skin symptoms of cutaneous T-cell lymphomathat has not responded to other therapies. ECP may be used to treatother blood cancers, and may also help reduce rejection aftertransplants.

Additionally, photosensitizing agent, such as porfimer sodium orPhotofrin®, may be used in PDT to treat or relieve the symptoms ofesophageal cancer and non-small cell lung cancer. Porfimer sodium mayrelieve symptoms of esophageal cancer when the cancer obstructs theesophagus or when the cancer cannot be satisfactorily treated with lasertherapy alone. Porfimer sodium may be used to treat non-small cell lungcancer in patients for whom the usual treatments are not appropriate,and to relieve symptoms in patients with non-small cell lung cancer thatobstructs the airways. Porfimer sodium may also be used for thetreatment of precancerous lesions in patients with Barrett esophagus, acondition that can lead to esophageal cancer.

Laser therapy may use high-intensity light to treat cancer and otherillnesses. Lasers can be used to shrink or destroy tumors orprecancerous growths. Lasers are most commonly used to treat superficialcancers (cancers on the surface of the body or the lining of internalorgans) such as basal cell skin cancer and the very early stages of somecancers, such as cervical, penile, vaginal, vulvar, and non-small celllung cancer.

Lasers may also be used to relieve certain symptoms of cancer, such asbleeding or obstruction. For example, lasers can be used to shrink ordestroy a tumor that is blocking a patient’s trachea (windpipe) oresophagus. Lasers also can be used to remove colon polyps or tumors thatare blocking the colon or stomach.

Laser therapy is often given through a flexible endoscope (a thin,lighted tube used to look at tissues inside the body). The endoscope isfitted with optical fibers (thin fibers that transmit light). It isinserted through an opening in the body, such as the mouth, nose, anus,or vagina. Laser light is then precisely aimed to cut or destroy atumor.

Laser-induced interstitial thermotherapy (LITT), or interstitial laserphotocoagulation, also uses lasers to treat some cancers. LITT issimilar to a cancer treatment called hyperthermia, which uses heat toshrink tumors by damaging or killing cancer cells. During LITT, anoptical fiber is inserted into a tumor. Laser light at the tip of thefiber raises the temperature of the tumor cells and damages or destroysthem. LITT is sometimes used to shrink tumors in the liver.

Laser therapy can be used alone, but most often it is combined withother treatments, such as surgery, chemotherapy, or radiation therapy.In addition, lasers can seal nerve endings to reduce pain after surgeryand seal lymph vessels to reduce swelling and limit the spread of tumorcells.

Lasers used to treat cancer may include carbon dioxide (CO₂) lasers,argon lasers, and neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers.Each of these can shrink or destroy tumors and can be used withendoscopes. CO₂ and argon lasers can cut the skin’s surface withoutgoing into deeper layers. Thus, they can be used to remove superficialcancers, such as skin cancer. In contrast, the Nd:YAG laser is morecommonly applied through an endoscope to treat internal organs, such asthe uterus, esophagus, and colon. Nd:YAG laser light can also travelthrough optical fibers into specific areas of the body during LITT.Argon lasers are often used to activate the drugs used in PDT.

For patients with systemic disease after a prostatectomy, systemicradiation therapy (e.g., samarium or strontium) may be combined withadditional treatment modalities such as adjuvant chemotherapy (e.g.,docetaxel, mitoxantrone, cabazitaxel, estramustine and prednisone),and/or hormone therapy including anti-androgen therapy (e.g., surgicalcastration, finasteride, flutamide, bicalutamide, niltamide,enzalutamide, ketoconazole and dutasteride); lutenizing hormonereleasing hormone (LHRH) agonists, (leuprolide, goserelin, triptorelinand histrelin) and/or LHRH antagonists, also known asgonadotropin-releasing hormone antagonists, (degarelix, ganirelix,cetrorelix and abarelix). Such patients would likely be treatedimmediately with radiation therapy either alone or in combination withone or more other treatment modalities in order to eliminate presumedmicro-metastatic disease.

Such patients can also be more closely monitored for signs of diseaseprogression. For patients with biochemical recurrence only (BCR-only orelevated PSA that does not rapidly become manifested as systemicdisease), only localized adjuvant therapy (e.g., radiation therapy ofthe prostate bed) or a short course of anti-androgen therapy wouldlikely be administered. For patients with no evidence of disease (NED),adjuvant therapy would not likely be recommended by their physicians inorder to avoid treatment-related side effects such as metabolic syndrome(e.g., hypertension, diabetes and/or weight gain), osteoporosis,proctitis, incontinence or impotence. Patients with NED could bedesignated for watchful waiting, or for no treatment. Patients withsystemic disease, but who have successive PSA increases, could bedesignated for watchful waiting, increased monitoring, or lower dose orshorter duration radiation therapy.

Target sequences can be grouped so that information obtained about theset of target sequences in the group can be used to make or assist inmaking a clinically relevant judgment such as a diagnosis, prognosis, ortreatment choice.

A patient report is also provided comprising a representation ofmeasured expression levels of a plurality of target sequences in abiological sample from the patient, wherein the representation comprisesexpression levels of target sequences corresponding to any one, two,three, four, five, six, eight, ten, twenty, or more of the targetsequences corresponding to a target selected from Table 1 or Table 2,the subsets described herein, or a combination thereof. In someembodiments, the representation of the measured expression level(s) maytake the form of a linear or nonlinear combination of expression levelsof the target sequences of interest. The patient report may furtherinclude a PORTOS. The patient report may be provided in a machine (e.g.,a computer) readable format and/or in a hard (paper) copy. The reportcan also include standard measurements of expression levels of saidplurality of target sequences from one or more sets of patients withknown disease status and/or outcome. The report can be used to informthe patient and/or treating physician of the expression levels of theexpressed target sequences, the likely medical diagnosis and/orimplications, and optionally may recommend a treatment modality (e.g.,radiation therapy) for the patient.

Also provided are representations of the gene expression profiles usefulfor treating, diagnosing, prognosticating, and otherwise assessingdisease. In some embodiments, these profile representations are reducedto a medium that can be automatically read by a machine such as computerreadable media (magnetic, optical, and the like). The articles can alsoinclude instructions for assessing the gene expression profiles in suchmedia. For example, the articles may comprise a readable storage formhaving computer instructions for comparing gene expression profiles ofthe portfolios of genes described above and/or calculating a PORTOSbased on the gene expression profiles. The articles may also have geneexpression profiles digitally recorded therein so that they may becompared with gene expression data from patient samples. Alternatively,the profiles can be recorded in different representational format. Agraphical recordation is one such format. Clustering algorithms canassist in the visualization of such data.

Prediction of Treatment Response to Radiation Therapy

A radiation response genomic signature can be utilized to predictwhether or not a patient who has prostate cancer will benefit fromradiation therapy. In particular, a post-operative radiation therapyoutcome score (PORTOS) can be calculated based on the levels ofexpression of a plurality of genes selected from Table 2 to determinewhether or not the subject is likely to benefit from post-operativeradiation therapy (see Examples). A PORTOS greater than 0 (i.e., highPORTOS) indicates that a subject will benefit from post-operativeradiation therapy, whereas a PORTOS of less than or equal to 0 (i.e.,low PORTOS) indicates that a subject will not benefit frompost-operative radiation therapy. Thus, patients with high PORTOSsignature scores are more likely to benefit from radiation treatmentafter surgery and may be prescribed or administered radiation therapy.

III. Experimental

Below are examples of specific embodiments for carrying out the presentinvention. The examples are offered for illustrative purposes only, andare not intended to limit the scope of the present invention in any way.

Efforts have been made to ensure accuracy with respect to numbers used(e.g., amounts, temperatures, etc.), but some experimental error anddeviation should, of course, be allowed for.

EXAMPLES Example 1: Development of a Genetic Signature to PredictPost-Operative Radiation Therapy Response in Prostate Cancer Patients.

DNA Damage Repair (DDR) genes and pathways are significantly associatedwith increased metastatic progression risk (Evans et al., Patient-LevelDNA Damage and Repair Pathway Profiles and Prognosis After Prostatectomyfor High-Risk Prostate Cancer, JAMA Oncol. 2016 Jan 7:1-10). DDR geneswere evaluated for their utility in a radiation response signatureprostate cancer patients following prostatectomy. An 1800 genecompilation from Gene Ontology (GO) and Gene Set Enrichment Analysis(GSEA) related to response to DNA damage and radiation and in the HumanExon Array platform were collected to identify a subset of genes havingthe most potential to predict response to radiation therapy (RT).

To develop a post-operative radiation therapy response signature, a 1:1matching was performed for patients treated and untreated with RT withina year in the MCI case-control prostatectomy cohort (Erho et al.,Discovery and validation of a prostate cancer genomic classifier thatpredicts early metastasis following radical prostatectomy. PLoS One2013; 8: e66855). Prostate cancer patients considered “treated” receivedadjuvant or salvage post-operative radiation after radical prostatectomyand before the primary endpoint of metastasis. Matching between treatedand untreated arms was performed on Gleason score, pre-operativeprostate specific antigen (PSA), positive surgical margins (SM),extracapsular extension (ECE), seminal vesicle invasion (SVI), lymphnode invasion (LNI), and androgen deprivation therapy (ADT). Gleasonscore was categorized into low (<7), intermediate (7), and high (8-10).Similarly, PSA was stratified into low (<10 ng/dL), intermediate (10-20ng/dL), and high (>20 ng/dL). SM, ECE, SVI, and LNI were treated asbinary variables and defined by the respective institutions. Theresulting matched training prostatectomy cohort (N=196) withwhole-genome expression profiles was used to develop the radiationresponse signature.

Using the training cohort, each of the 1800 genes was ranked in order ofits univariate interaction p-value in a Cox proportional hazards model.This ranked gene list was used to train a ridge-penalized Cox model,using metastasis as the endpoint, and with treatment and the interactionterms of treatment and each gene as the variables. Feature selection wasperformed by varying the number of included features from 10 to 25 (9 to24 genes in addition to treatment) in order to range from approximately10 to 4 events per variable in the training cohort. The final gene listwas the model that minimized the interaction p-value in the trainingcohort. The predictions from the model are calculated by taking thedifference of the predictions without RT and with RT, and converting tobinary scores using a cutoff of 0. The resulting score is thePost-Operative Radiation Therapy Outcome Score (PORTOS) where patientswith scores greater than 0 (high PORTOS) benefit from treatment, andpatients with scores less than or equal to 0 (low PORTOS) do not benefitfrom treatment. As a result a 24-gene model was developed usingridge-penalized Cox regression to model the interactions of the genesand radiation therapy to generate the PORTOS [Table 2]. The model wasthen applied to the independent validation cohort.

TABLE 2 A list of the 24 genes in PORTOS model with their regressioncoefficients Gene Coefficient Gene Coefficient DRAM1 -0.102 HCLS1 -0.008KRT14 -0.847 DTL 1.161 PTPN22 -1.029 IL7R 0.135 ZMAT3 0.118 UBA7 0.291ARHGAP15 -1.114 NEK1 0.678 IL1B -1.502 CDKN2AIP 0.466 ANLN -1.233 APEX20.671 RPS27A 0.364 KIF23 1.01 MUM1 0.444 SULF2 -0.288 TOP2A 1.378 PLK2-1.294 GNG11 0.41 EME1 1.39 CDKN3 -0.848 BIN2 0.529

Example 2: PORTOS Is Predictive of Response to Radiation Therapy inProstate Cancer Patients

In the matched training cohort, PORTOS was able to predict response toradiation therapy (RT) as evidenced by the significant interaction term(p<0.0001, FIG. 1A). In patients with high scores (PORTOS>0), treatedpatients had better outcomes than untreated patients with a 10-yearmetastasis rate of 5% in RT treated patients and 63% in untreatedpatients (p<0.0001, HR=0.12 [0.033-0.41], FIGS. 1B and 2A), whereas inpatients with low scores (PORTOS<0), untreated patients had betteroutcomes with a 10-year metastasis rate of 31%, compared to 57% in RTtreated patients (p=0.0001, HR=2.5 [1.6-4.1], FIGS. 1B and 2B). Theseresults showed that the PORTOS of the present invention was useful forpredicting benefit from post-operative RT in patients with prostatecancer. These results also indicated that the methods of the presentinvention are useful for treating prostate cancer. These results furtherindicated that methods of the present invention are useful forpredicting response to post-operative radiation therapy and treating asubject for prostate cancer.

Example 3: PORTOS Is Predictive of Response to Radiation Therapy in anIndependent Validation of the Model

To independently validate the model, a matched cohort of treated anduntreated radiation therapy (RT) patients was designed using a pooledcohort from four clinical sites (MCII, THU, TJU and DVA). These resultswere confirmed in an independent matched validation cohort, with asignificant interaction term (p<0.05, FIG. 1C). Within the high PORTOSgroup, patients treated with RT had better outcomes than untreatedpatients (p=0.01, HR=0.19 [0.048-0.78], FIG. 2C), with a 10-yearmetastasis rate of 4% in RT treated patients and 31% in untreatedpatients (FIG. 1D). Within the low PORTOS group, untreated patients hadoutcomes similar as treated patients (p=0.77, HR=0.92 [0.56-1.5], FIG.2D) with 10-year metastasis rate of 31% in RT treated patients and 32%in untreated patients (FIG. 1D).

These results provide further evidence that patients with high scoresare more likely to benefit from radiation treatment after surgery. Theseresults showed that the PORTOS was useful for predicting benefit frompost-operative RT in patients with prostate cancer. These resultsfurther indicated that methods of the present invention are useful forpredicting response to post-operative radiation therapy and treating asubject for prostate cancer.

Example 4: PORTOS is an Independent Predictor of Response to RadiationTherapy After Adjusting for Clinical Variables

To determine whether PORTOS is predictive, multivariable interactionanalyses (MVA) to examine the interaction between PORTOS scores and RTtreatment in a pooled set from multiple cohorts from differentinstitutes was performed [Table 3]. Due to the differences in thebaseline risks of cohorts, MVA adjusting was performed for clinicalvariables and institute. PORTOS was significantly interacting with RT (p<0.05).

These results provide further evidence that patients with high scoresare more likely to benefit from radiation treatment after surgery. Theseresults showed that the PORTOS was useful for predicting benefit frompost-operative RT in patients with prostate cancer. These resultsfurther indicated that methods of the present invention are useful forpredicting response to post-operative radiation therapy and treating asubject for prostate cancer.

TABLE 3 MVA of PORTOS adjusted for clinical variables to predictresponse to RT Covariate P-value HR [95% CI] RT 0.00411 2.49 [1.34-4.65]PORTOS 8.26E-07 0.36 [0.24-0.54] PSA < 10 Reference 10-20 0.179 0.8[0.58-1.11] > 20 0.547 1.13 [0.76-1.68] Gleason <7 Reference 7 0.1344.57 [0.63-33.39] 8-10 0.0166 11.38 [1.56-83.3] SMS 0.787 1.04[0.77-1.41] SVI 4.37E-05 1.89 [1.39-2.56] ECE 0.269 1.22 [0.86-1.74] LNI0.00226 1.69 [1.21-2.36] ADT 0.0102 2.13 [1.2-3.8] Study DVA ReferenceJHMI 9.86E-06 11.6 [3.91-34.41] Mayo Val 0.000273 6.32 [2.34-17.04] TJU0.535 1.5 [0.42-5.43] RT:PORTOS 0.0203 2.74 [1.17-6.41]

Example 5: Univariate and Pairwise Analysis of the 24 Target Genes inthe Genetic Signature to Predict Post-Operative Radiation TherapyResponse in Prostate Cancer Patients Across Different Endpoints

The 24 targets in the genetic signature described in Example 1 wereassessed for their performance across a range of different metrics andendpoints in both the training and validation cohorts.

Table 4 shows univariate (UVA) and pairwise (MVA) analysis of theinteraction between RT treatment and individual genes in the geneticsignature in Example 1. Table 5 shows univariate (UVA) and pairwise(MVA) analysis of the interaction between pairwise combinations of genesin the genetic signature and radiation therapy (RT) treatment adjustedfor clinical variables. The associated p-value provided in Table 4 and 5gives a measure of the statistical significance of the correspondingmetric.

As shown in Tables 4 and 5, the performance of the 24 genes in thegenetic signature, individually and as pairwise combinations, werestatistically significant in the training and validation cohorts forpredicting response to RT treatment. These results showed that thetargets of the present invention are useful for predicting benefit frompost-operative RT in patients with prostate cancer. These results alsoindicated that the methods of the present invention are useful fortreating prostate cancer. These results further indicated that methodsof the present invention are useful for predicting response topost-operative radiation therapy and treating a subject for prostatecancer.

TABLE 4 Univariate and Multivariate Analysis of the 24 Target Genes fromthe Genetic Signature with Associated P-values. Gene UVA p-value ofinteraction of treatment and gene in Training Cohort UVA p-value ofinteraction of treatment and gene in Validation Cohort MVA p-value ofinteraction of treatment and gene adjusting for clinical variablesPooled in Validation Cohort DRAM1 0.001 0.361 0.524 KRT14 0.001 0.5490.046 PTPN22 0.005 0.407 0.004 ZMAT3 0.012 0.275 0.927 ARHGAP15 0.0130.478 0.178 IL1B 0.013 0.611 0.891 ANLN 0.020 0.492 0.008 RPS27A 0.0210.386 0.228 MUM1 0.029 0.833 0.530 TOP2A 0.032 0.083 0.239 GNG11 0.0350.171 0.251 CDKN3 0.036 0.691 0.087 HCLS1 0.042 0.778 0.797 DTL 0.0470.607 0.012 IL7R 0.050 0.829 0.076 UBA7 0.050 0.905 0.435 NEK1 0.0530.506 0.893 CDKN2AIP 0.057 0.589 0.323 APEX2 0.059 0.644 0.703 KIF230.059 0.437 0.154 SULF2 0.061 0.173 0.178 PLK2 0.065 0.231 0.242 EME10.067 0.031 0.006 BIN2 0.071 0.009 0.000

TABLE 5 Univariate and Multivariable Analysis of pairwise combinationsof the 24 Genes from the Genetic Signature with Associated P-values.Gene 1 Gene 2 UVA p-value of interaction of treatment and Genes 1 and 2in Training Cohort UVA p-value of interaction of treatment and Genes 1and 2 in Validation Cohort MVA p-value of interaction of treatment andgenes 1 and 2 adjusting for clinical variables in Pooled ValidationCohort DRAM1 KRT14 0.000 0.596 0.058 DRAM1 PTPN22 0.002 0.370 0.014DRAM1 ZMAT3 0.655 0.081 0.667 DRAM1 ARHGAP15 0.005 0.448 0.705 DRAM1IL1B 0.007 0.601 0.807 DRAM1 ANLN 0.006 0.370 0.115 DRAM1 RPS27A 0.0010.190 0.663 DRAM1 MUM1 0.002 0.979 0.315 DRAM1 TOP2A 0.044 0.075 0.911DRAM1 GNG11 0.007 0.220 0.363 DRAM1 CDKN3 0.016 0.807 0.163 DRAM1 HCLS 10.001 0.393 0.911 DRAM1 DTL 0.015 0.687 0.028 DRAM1 IL7R 0.434 0.9940.120 DRAM1 UBA7 0.452 0.787 0.751 DRAM1 NEK1 0.031 0.568 0.449 DRAM1CDKN2AIP 0.019 0.516 0.198 DRAM1 APEX2 0.017 0.487 0.249 DRAM1 KIF230.148 0.527 0.542 DRAM1 SULF2 0.008 0.333 0.368 DRAM1 PLK2 0.039 0.2670.041 DRAM1 EME1 0.033 0.041 0.018 DRAM1 BIN2 0.298 0.015 0.000 KRT14PTPN22 0.000 0.882 0.838 KRT14 ZMAT3 0.002 0.602 0.055 KRT14 ARHGAP150.000 0.967 0.196 KRT14 IL1B 0.000 0.664 0.287 KRT14 ANLN 0.000 0.3570.276 KRT14 RPS27A 0.000 0.688 0.087 KRT14 MUM1 0.000 0.616 0.131 KRT14TOP2A 0.844 0.360 0.456 KRT14 GNG11 0.000 0.363 0.041 KRT14 CDKN3 0.0000.312 0.248 KRT14 HCLS 1 0.001 0.547 0.055 KRT14 DTL 0.000 0.506 0.009KRT14 IL7R 0.004 0.435 0.023 KRT14 UBA7 0.002 0.507 0.054 KRT14 NEK10.000 0.520 0.343 KRT14 CDKN2AIP 0.000 0.832 0.271 KRT14 APEX2 0.0000.719 0.142 KRT14 KIF23 0.074 0.314 0.046 KRT14 SULF2 0.000 0.368 0.039KRT14 PLK2 0.000 0.106 0.809 KRT14 EME1 0.000 0.035 0.003 KRT14 BIN20.011 0.133 0.003 PTPN22 ZMAT3 0.010 0.337 0.010 PTPN22 ARHGAP15 0.0020.368 0.105 PTPN22 IL1B 0.001 0.601 0.228 PTPN22 ANLN 0.002 0.102 0.004PTPN22 RPS27A 0.001 0.312 0.007 PTPN22 MUM1 0.001 0.511 0.007 PTPN22TOP2A 0.363 0.071 0.252 PTPN22 GNG11 0.001 0.785 0.029 PTPN22 CDKN30.001 0.307 0.005 PTPN22 HCLS1 0.005 0.412 0.011 PTPN22 DTL 0.000 0.7210.610 PTPN22 IL7R 0.020 0.502 0.022 PTPN22 UBA7 0.019 0.379 0.005 PTPN22NEK1 0.003 0.842 0.016 PTPN22 CDKN2AIP 0.001 0.304 0.003 PTPN22 APEX20.001 0.340 0.004 PTPN22 KIF23 0.281 0.851 0.080 PTPN22 SULF2 0.0020.819 0.041 PTPN22 PLK2 0.003 0.601 0.003 PTPN22 EME1 0.001 0.207 0.989PTPN22 BIN2 0.040 0.610 0.304 ZMAT3 ARHGAP15 0.027 0.409 0.706 ZMAT3IL1B 0.022 0.529 0.795 ZMAT3 ANLN 0.042 0.495 0.153 ZMAT3 RPS27A 0.1420.338 0.817 ZMAT3 MUM1 0.176 0.857 0.377 ZMAT3 TOP2A 0.023 0.085 0.967ZMAT3 GNG11 0.136 0.280 0.379 ZMAT3 CDKN3 0.073 0.729 0.171 ZMAT3 HCLS 10.021 0.289 0.558 ZMAT3 DTL 0.117 0.659 0.023 ZMAT3 IL7R 0.013 0.9820.185 ZMAT3 UBA7 0.017 0.917 0.906 ZMAT3 NEK1 0.101 0.575 0.521 ZMAT3CDKN2AIP 0.145 0.503 0.252 ZMAT3 APEX2 0.156 0.600 0.326 ZMAT3 KIF230.033 0.562 0.516 ZMAT3 SULF2 0.401 0.331 0.207 ZMAT3 PLK2 0.097 0.2370.036 ZMAT3 EME1 0.118 0.038 0.014 ZMAT3 BIN2 0.023 0.020 0.001 ARHGAP15IL1B 0.002 0.509 0.717 ARHGAP15 ANLN 0.005 0.259 0.274 ARHGAP15 RPS27A0.001 0.370 0.525 ARHGAP15 MUM1 0.002 0.508 0.415 ARHGAP15 TOP2A 0.3270.052 0.566 ARHGAP15 GNG11 0.001 0.847 0.965 ARHGAP15 CDKN3 0.004 0.5230.320 ARHGAP15 HCLS1 0.012 0.482 0.692 ARHGAP15 DTL 0.001 0.559 0.340ARHGAP15 IL7R 0.059 0.468 0.835 ARHGAP15 UBA7 0.048 0.480 0.566 ARHGAP15NEK1 0.004 0.748 0.327 ARHGAP15 CDKN2AIP 0.002 0.341 0.244 ARHGAP15APEX2 0.000 0.314 0.305 ARHGAP15 KIF23 0.475 0.722 0.988 ARHGAP15 SULF20.006 0.767 0.898 ARHGAP15 PLK2 0.006 0.577 0.069 ARHGAP15 EME1 0.0010.329 0.180 ARHGAP15 BIN2 0.142 0.793 0.232 IL1B ANLN 0.004 0.847 0.813II1B RPS27A 0.003 0.508 0.637 IL1B MUM1 0.004 0.605 0.531 IL1B TOP2A0.940 0.064 0.347 IL1B GNG11 0.002 0.912 0.992 IL1B CDKN3 0.004 0.7320.727 IL1B HCLS1 0.013 0.613 0.782 IL1B DTL 0.001 0.475 0.807 IL1B IL7R0.032 0.666 0.932 IL1B UBA7 0.031 0.730 0.737 IL1B NEK1 0.005 0.7510.403 IL1B CDKN2AIP 0.003 0.537 0.329 IL1B APEX2 0.001 0.398 0.392 IL1BKIF23 0.103 0.764 0.936 IL1B SULF2 0.007 0.743 0.870 IL1B PLK2 0.0040.422 0.200 IL1B EME1 0.001 0.385 0.444 IL1B BIN2 0.028 0.815 0.487 ANLNRPS27A 0.003 0.530 0.142 ANLN MUM1 0.004 0.585 0.080 ANLN TOP2A 0.3460.061 0.587 ANLN GNG11 0.001 0.941 0.307 ANLN CDKN3 0.006 0.794 0.098ANLN HCLS1 0.018 0.485 0.128 ANLN DTL 0.000 0.864 0.693 ANLN IL7R 0.1030.868 0.663 ANLN UBA7 0.097 0.741 0.138 ANLN NEK1 0.012 0.785 0.234 ANLNCDKN2AIP 0.006 0.860 0.132 ANLN APEX2 0.000 0.677 0.069 ANLN KIF23 0.4310.860 0.060 ANLN SULF2 0.007 0.433 0.104 ANLN PLK2 0.009 0.733 0.018ANLN EME1 0.001 0.108 0.334 ANLN BIN2 0.215 0.375 0.836 RPS27A MUM10.004 0.737 0.233 RPS27A TOP2A 0.114 0.126 0.918 RPS27A GNG11 0.0040.466 0.684 RPS27A CDKN3 0.004 0.918 0.118 RPS27A HCLS1 0.018 0.3890.696 RPS27A DTL 0.007 0.698 0.044 RPS27A IL7R 0.430 0.879 0.498 RPS27AUBA7 0.527 0.541 0.577 RPS27A NEK1 0.016 0.659 0.394 RPS27A CDKN2AIP0.007 0.523 0.208 RPS27A APEX2 0.009 0.432 0.210 RPS27A KIF23 0.5010.652 0.702 RPS27A SULF2 0.003 0.763 0.684 RPS27A PLK2 0.017 0.257 0.029RPS27A EME1 0.013 0.063 0.028 RPS27A BIN2 0.976 0.024 0.007 MUM1 TOP2A0.036 0.063 0.751 MUM1 GNG11 0.005 0.221 0.828 MUM1 CDKN3 0.004 0.8810.077 MUM1 HCLS1 0.025 0.829 0.284 MUM1 DTL 0.010 0.808 0.137 MUM1 IL7R0.330 0.584 0.673 MUM1 UBA7 0.469 0.817 0.391 MUM1 NEK1 0.025 0.6070.249 MUM1 CDKN2AIP 0.007 0.621 0.096 MUM1 APEX2 0.011 0.796 0.152 MUM1KIF23 0.449 0.474 0.997 MUM1 SULF2 0.001 0.248 0.792 MUM1 PLK2 0.0150.257 0.023 MUM1 EME1 0.016 0.034 0.045 MUM1 BIN2 0.931 0.007 0.020TOP2A GNG11 0.107 0.115 0.978 TOP2A CDKN3 0.419 0.089 0.681 TOP2A HCLS10.032 0.083 0.949 TOP2A DTL 0.220 0.155 0.556 TOP2A IL7R 0.026 0.1890.737 TOP2A UBA7 0.021 0.085 0.966 TOP2A NEK1 0.546 0.112 0.752 TOP2ACDKN2AIP 0.305 0.282 0.813 TOP2A APEX2 0.138 0.131 0.954 TOP2A KIF230.004 0.100 0.972 TOP2A SULF2 0.064 0.068 0.883 TOP2A PLK2 0.402 0.3570.237 TOP2A EME1 0.413 0.278 0.632 TOP2A BIN2 0.013 0.390 0.542 GNG11CDKN3 0.002 0.277 0.485 GNG11 HCLS1 0.032 0.166 0.375 GNG11 DTL 0.0090.544 0.035 GNG11 IL7R 0.268 0.269 0.185 GNG11 UBA7 0.366 0.231 0.592GNG11 NEK1 0.010 0.307 0.920 GNG11 CDKN2AIP 0.002 0.755 0.670 GNG11APEX2 0.011 0.528 0.878 GNG11 KIF23 0.772 0.197 0.369 GNG11 SULF2 0.0070.038 0.179 GNG11 PLK2 0.007 0.120 0.063 GNG11 EME1 0.025 0.008 0.010GNG11 BIN2 0.691 0.017 0.009 CDKN3 HCLS1 0.033 0.694 0.157 CDKN3 DTL0.004 0.509 0.428 CDKN3 IL7R 0.159 0.312 0.664 CDKN3 UBA7 0.111 0.6540.211 CDKN3 NEK1 0.020 0.561 0.237 CDKN3 CDKN2AIP 0.016 0.787 0.087CDKN3 APEX2 0.000 0.724 0.081 CDKN3 KIF23 0.469 0.340 0.446 CDKN3 SULF20.015 0.571 0.221 CDKN3 PLK2 0.012 0.321 0.024 CDKN3 EME1 0.002 0.0180.251 CDKN3 BIN2 0.203 0.062 0.782 HCLS1 DTL 0.044 0.605 0.028 HCLS1IL7R 0.054 0.828 0.175 HCLS1 UBA7 0.059 0.894 0.798 HCLS1 NEK1 0.0500.500 0.467 HCLS1 CDKN2AIP 0.051 0.596 0.207 HCLS1 APEX2 0.056 0.6480.265 HCLS1 KIF23 0.065 0.437 0.537 HCLS1 SULF2 0.052 0.173 0.283 HCLS1PLK2 0.063 0.230 0.038 HCLS1 EME1 0.065 0.032 0.016 HCLS1 BIN2 0.0800.008 0.001 DTL IL7R 0.210 0.407 0.005 DTL UBA7 0.211 0.596 0.026 DTLNEK1 0.015 0.102 0.151 DTL CDKN2AIP 0.006 0.544 0.152 DTL APEX2 0.0080.526 0.199 DTL KIF23 0.997 0.595 0.109 DTL SULF2 0.009 0.533 0.033 DTLPLK2 0.005 0.169 0.492 DTL EME1 0.012 0.063 0.004 DTL BIN2 0.413 0.2990.001 IL7R UBA7 0.017 0.682 0.424 IL7R NEK1 0.127 0.486 0.839 IL7RCDKN2AIP 0.302 0.661 0.648 IL7R APEX2 0.246 0.995 0.977 IL7R KIF23 0.0110.347 0.187 IL7R SULF2 0.893 0.210 0.027 IL7R PLK2 0.158 0.170 0.091IL7R EME1 0.150 0.020 0.003 IL7R BIN2 0.016 0.049 0.002 UBA7 NEK1 0.1140.548 0.517 UBA7 CDKN2AIP 0.283 0.701 0.248 UBA7 APEX2 0.318 0.704 0.267UBA7 KIF23 0.030 0.342 0.650 UBA7 SULF2 0.934 0.139 0.552 UBA7 PLK20.141 0.263 0.032 UBA7 EME1 0.200 0.021 0.014 UBA7 BIN2 0.020 0.0290.016 NEK1 CDKN2AIP 0.025 0.868 0.255 NEK1 APEX2 0.003 0.690 0.303 NEK1KIF23 0.638 0.471 0.637 NEK1 SULF2 0.018 0.271 0.619 NEK1 PLK2 0.0040.122 0.017 NEK1 EME1 0.005 0.031 0.172 NEK1 BIN2 0.147 0.065 0.445CDKN2AIP APEX2 0.002 0.553 0.110 CDKN2AIP KIF23 0.777 0.957 0.686CDKN2AIP SULF2 0.016 0.947 0.417 CDKN2AIP PLK2 0.013 0.305 0.008CDKN2AIP EME1 0.004 0.109 0.155 CDKN2AIP BIN2 0.465 0.381 0.377 APEX2KIF23 0.992 0.656 0.809 APEX2 SULF2 0.010 0.911 0.510 APEX2 PLK2 0.0100.246 0.013 APEX2 EME1 0.024 0.088 0.116 APEX2 BIN2 0.593 0.175 0.221KIF23 SULF2 0.198 0.371 0.405 KIF23 PLK2 0.455 0.160 0.092 KIF23 EME10.587 0.059 0.031 KIF23 BIN2 0.032 0.041 0.023 SULF2 PLK2 0.036 0.1630.070 SULF2 EME1 0.021 0.022 0.015 SULF2 BIN2 0.464 0.002 0.000 PLK2EME1 0.006 0.018 0.642 PLK2 BIN2 0.249 0.072 0.291 EME1 BIN2 0.353 0.0050.001

While the preferred embodiments of the invention have been illustratedand described, it will be appreciated that various changes can be madetherein without departing from the spirit and scope of the invention.

1-30. (canceled)
 31. A method for treating a subject having prostatecancer, comprising: a) obtaining a post-operative radiation therapyoutcome score (PORTOS) that has been calculated using a level ofexpression of a plurality of genes in the biological sample, whereinsaid plurality of genes comprises one or more genes selected from thegroup consisting of DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1,CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2; b) determiningwhether or not the subject is likely to benefit from post-operativeradiation therapy based on the PORTOS score, wherein a PORTOS greaterthan 0 indicates that the subject will benefit from the post-operativeradiation therapy and a PORTOS less than or equal to 0 indicates thatthe subject will not benefit from the post-operative radiation therapy;and c) if the PORTOS indicates that the subject will benefit from theradiation therapy, then administering the post-operative radiationtherapy to the subject, and if the PORTOS does not indicate that thesubject will benefit from the post-operative radiation therapy, thenadministering a cancer treatment other than the post-operative radiationtherapy to the subject.
 32. The method of claim 31, wherein the subjecthas previously undergone a radical prostatectomy.
 33. The method ofclaim 31, wherein the prostate cancer has not metastasized.
 34. Themethod of claim 31, wherein the biological sample is a biopsy.
 35. Themethod of claim 31, wherein the biological sample is a tumor sample. 36.The method of claim 31, wherein the subject is a human being.
 37. Themethod of claim 31, wherein the level of expression has been measured byperforming microarray analysis, polymerase chain reaction (PCR), reversetranscriptase polymerase chain reaction (RT-PCR), a Northern blot, orserial analysis of gene expression (SAGE).
 38. The method of claim 31,wherein said administering post-operative radiation therapy to thesubject, or administering a cancer treatment other than thepost-operative radiation therapy to the subject further comprisesperforming chemotherapy, immunotherapy, hormonal therapy, biologictherapy, or any combination thereof.
 39. The method of claim 31, whereinthe PORTOS indicates that the subject will benefit from the radiationtherapy, and administering the post-operative radiation therapy to thesubject.
 40. The method of claim 31, wherein the plurality of genescomprises at least 2 genes selected from the group consisting of DRAM1,KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11,CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2,PLK2, EME1, and BIN2.
 41. The method of claim 31, wherein the pluralityof genes comprises at least 5 genes selected from the group consistingof DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1,TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2,KIF23, SULF2, PLK2, EME1, and BIN2.
 42. The method of claim 31, whereinthe plurality of genes comprises at least 10 genes selected from thegroup consisting of DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN,RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1,CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2.
 43. The method ofclaim 31, wherein the plurality of genes comprises at least 15 genesselected from the group consisting of DRAM1, KRT14, PTPN22, ZMAT3,ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL,IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2.44. The method of claim 31, wherein the plurality of genes comprises atleast 20 genes selected from the group consisting of DRAM1, KRT14,PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3,HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1,and BIN2.
 45. The method of claim 31, wherein the plurality of genescomprises one or more genes selected from the group consisting of KRT14,PTPN22, ANLN, DTL, EME1, and BIN2.
 46. The method of claim 31, whereinthe plurality of genes comprises KRT14, PTPN22, ANLN, DTL, EME1, andBIN2.
 47. The method of claim 31, wherein the plurality of genescomprises one or more genes selected from the group consisting ofARHGAP15, BIN2, DRAM1, HCLS1, IL7R, PTPN2, and SULF2.
 48. The method ofclaim 31, wherein the plurality of genes comprises ARHGAP15, BIN2,DRAM1, HCLS1, IL7R, PTPN2, and SULF2.
 49. The method of claim 31,wherein the plurality of genes comprises a pair of genes selected from:DRAM1 and BIN2; SULF2 and BIN2; ZMAT3 and BIN2; HCLS1 and BIN2; DTL andBIN2; EME1 and BIN2; IL7R and BIN2; KRT14 and EME1; KRT14 and BIN2;PTPN22 and CDKN2AIP; PTPN22 and PLK2; IL7R and EME1; PTPN22 and ANLN;PTPN22 and APEX2; DTL and EME1; PTPN22 and CDKN3; PTPN22 and UBA7; DTLand IL7R; PTPN22 and RPS27A; PTPN22 and MUM1; RPS27A and BIN2; CDKN2AIPand PLK2; KRT14 and DTL; GNG11 and BIN2; PTPN22 and ZMAT3; GNG11 andEME1; PTPN22 and HCLS1; APEX2 and PLK2; DRAM1 and PTPN22; ZMAT3 andEME1; UBA7 and EME1; SULF2 and EME1; PTPN22 and NEK1; HCLS1 and EME1;UBA7 and BIN2; NEK1 and PLK2; DRAM1 and EME1; ANLN and PLK2; MUM1 andBIN2; PTPN22 and IL7R; KRT14 and IL7R; ZMAT3 and DTL; MUM1 and PLK2;KIF23 and BIN2; CDKN3 and PLK2; DTL and UBA7; IL7R and SULF2; DRAM1 andDTL; RPS27A and EME1; HCLS1 and DTL; PTPN22 and GNG11; RPS27A and PLK2;KIF23 and EME1; UBA7 and PLK2; DTL and SULF2; GNG11 and DTL; ZMAT3 andPLK2; HCLS1 and PLK2; KRT14 and SULF2; DRAM1 and PLK2; KRT14 and GNG11;PTPN22 and SULF2; RPS27A and DTL; MUM1 and EME1; and KRT14 and KIF23.50. The method of claim 31, wherein the post-operative radiation therapyis selected from the group consisting of intensity-modulated radiationtherapy (IMRT), image-guided radiation therapy (IGRT), stereotacticradiosurgery (SRS), stereotactic body radiation therapy (SBRT), protontherapy, and brachytherapy.